<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Prins, Bram P</style></author><author><style face="normal" font="default" size="100%">Mead, Timothy J</style></author><author><style face="normal" font="default" size="100%">Brody, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Sveinbjornsson, Gardar</style></author><author><style face="normal" font="default" size="100%">Ntalla, Ioanna</style></author><author><style face="normal" font="default" size="100%">Bihlmeyer, Nathan A</style></author><author><style face="normal" font="default" size="100%">van den Berg, Marten</style></author><author><style face="normal" font="default" size="100%">Bork-Jensen, Jette</style></author><author><style face="normal" font="default" size="100%">Cappellani, Stefania</style></author><author><style face="normal" font="default" size="100%">Van Duijvenboden, Stefan</style></author><author><style face="normal" font="default" size="100%">Klena, Nikolai T</style></author><author><style face="normal" font="default" size="100%">Gabriel, George C</style></author><author><style face="normal" font="default" size="100%">Liu, Xiaoqin</style></author><author><style face="normal" font="default" size="100%">Gulec, Cagri</style></author><author><style face="normal" font="default" size="100%">Grarup, Niels</style></author><author><style face="normal" font="default" size="100%">Haessler, Jeffrey</style></author><author><style face="normal" font="default" size="100%">Hall, Leanne M</style></author><author><style face="normal" font="default" size="100%">Iorio, Annamaria</style></author><author><style face="normal" font="default" size="100%">Isaacs, Aaron</style></author><author><style face="normal" font="default" size="100%">Li-Gao, Ruifang</style></author><author><style face="normal" font="default" size="100%">Lin, Honghuang</style></author><author><style face="normal" font="default" size="100%">Liu, Ching-Ti</style></author><author><style face="normal" font="default" size="100%">Lyytikäinen, Leo-Pekka</style></author><author><style face="normal" font="default" size="100%">Marten, Jonathan</style></author><author><style face="normal" font="default" size="100%">Mei, Hao</style></author><author><style face="normal" font="default" size="100%">Müller-Nurasyid, Martina</style></author><author><style face="normal" font="default" size="100%">Orini, Michele</style></author><author><style face="normal" font="default" size="100%">Padmanabhan, Sandosh</style></author><author><style face="normal" font="default" size="100%">Radmanesh, Farid</style></author><author><style face="normal" font="default" size="100%">Ramirez, Julia</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Schwartz, Molly</style></author><author><style face="normal" font="default" size="100%">van Setten, Jessica</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">Verweij, Niek</style></author><author><style face="normal" font="default" size="100%">Warren, Helen R</style></author><author><style face="normal" font="default" size="100%">Weiss, Stefan</style></author><author><style face="normal" font="default" size="100%">Alonso, Alvaro</style></author><author><style face="normal" font="default" size="100%">Arnar, David O</style></author><author><style face="normal" font="default" size="100%">Bots, Michiel L</style></author><author><style face="normal" font="default" size="100%">de Boer, Rudolf A</style></author><author><style face="normal" font="default" size="100%">Dominiczak, Anna F</style></author><author><style face="normal" font="default" size="100%">Eijgelsheim, Mark</style></author><author><style face="normal" font="default" size="100%">Ellinor, Patrick T</style></author><author><style face="normal" font="default" size="100%">Guo, Xiuqing</style></author><author><style face="normal" font="default" size="100%">Felix, Stephan B</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Heckbert, Susan R</style></author><author><style face="normal" font="default" size="100%">Huang, Paul L</style></author><author><style face="normal" font="default" size="100%">Jukema, J W</style></author><author><style face="normal" font="default" size="100%">Kähönen, Mika</style></author><author><style face="normal" font="default" size="100%">Kors, Jan A</style></author><author><style face="normal" font="default" size="100%">Lambiase, Pier D</style></author><author><style face="normal" font="default" size="100%">Launer, Lenore J</style></author><author><style face="normal" font="default" size="100%">Li, Man</style></author><author><style face="normal" font="default" size="100%">Linneberg, Allan</style></author><author><style face="normal" font="default" size="100%">Nelson, Christopher P</style></author><author><style face="normal" font="default" size="100%">Pedersen, Oluf</style></author><author><style face="normal" font="default" size="100%">Perez, Marco</style></author><author><style face="normal" font="default" size="100%">Peters, Annette</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Psaty, Bruce M</style></author><author><style face="normal" font="default" size="100%">Raitakari, Olli T</style></author><author><style face="normal" font="default" size="100%">Rice, Kenneth M</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Sinner, Moritz F</style></author><author><style face="normal" font="default" size="100%">Soliman, Elsayed Z</style></author><author><style face="normal" font="default" size="100%">Spector, Tim D</style></author><author><style face="normal" font="default" size="100%">Strauch, Konstantin</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Tinker, Andrew</style></author><author><style face="normal" font="default" size="100%">Trompet, Stella</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André</style></author><author><style face="normal" font="default" size="100%">Vaartjes, Ilonca</style></author><author><style face="normal" font="default" size="100%">van der Meer, Peter</style></author><author><style face="normal" font="default" size="100%">Völker, Uwe</style></author><author><style face="normal" font="default" size="100%">Völzke, Henry</style></author><author><style face="normal" font="default" size="100%">Waldenberger, Melanie</style></author><author><style face="normal" font="default" size="100%">Wilson, James G</style></author><author><style face="normal" font="default" size="100%">Xie, Zhijun</style></author><author><style face="normal" font="default" size="100%">Asselbergs, Folkert W</style></author><author><style face="normal" font="default" size="100%">Dörr, Marcus</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Hansen, Torben</style></author><author><style face="normal" font="default" size="100%">Kääb, Stefan</style></author><author><style face="normal" font="default" size="100%">Kanters, Jørgen K</style></author><author><style face="normal" font="default" size="100%">Kooperberg, Charles</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho</style></author><author><style face="normal" font="default" size="100%">Lin, Henry J</style></author><author><style face="normal" font="default" size="100%">Lubitz, Steven A</style></author><author><style face="normal" font="default" size="100%">Mook-Kanamori, Dennis O</style></author><author><style face="normal" font="default" size="100%">Conti, Francesco J</style></author><author><style face="normal" font="default" size="100%">Newton-Cheh, Christopher H</style></author><author><style face="normal" font="default" size="100%">Rosand, Jonathan</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Samani, Nilesh J</style></author><author><style face="normal" font="default" size="100%">Sinagra, Gianfranco</style></author><author><style face="normal" font="default" size="100%">Smith, Blair H</style></author><author><style face="normal" font="default" size="100%">Holm, Hilma</style></author><author><style face="normal" font="default" size="100%">Stricker, Bruno H</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">Sotoodehnia, Nona</style></author><author><style face="normal" font="default" size="100%">Apte, Suneel S</style></author><author><style face="normal" font="default" size="100%">van der Harst, Pim</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Munroe, Patricia B</style></author><author><style face="normal" font="default" size="100%">Arking, Dan E</style></author><author><style face="normal" font="default" size="100%">Lo, Cecilia W</style></author><author><style face="normal" font="default" size="100%">Jamshidi, Yalda</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.</style></title><secondary-title><style face="normal" font="default" size="100%">Genome Biol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Genome Biol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">ADAMTS Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">African Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Connexin 43</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrocardiography</style></keyword><keyword><style  face="normal" font="default" size="100%">European Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Profiling</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Conduction System</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardium</style></keyword><keyword><style  face="normal" font="default" size="100%">Open Reading Frames</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Whole Exome Sequencing</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 07 17</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">19</style></volume><pages><style face="normal" font="default" size="100%">87</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/30012220?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">van Setten, Jessica</style></author><author><style face="normal" font="default" size="100%">Brody, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Jamshidi, Yalda</style></author><author><style face="normal" font="default" size="100%">Swenson, Brenton R</style></author><author><style face="normal" font="default" size="100%">Butler, Anne M</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Del Greco, Fabiola M</style></author><author><style face="normal" font="default" size="100%">Evans, Daniel S</style></author><author><style face="normal" font="default" size="100%">Gibson, Quince</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Kerr, Kathleen F</style></author><author><style face="normal" font="default" size="100%">Krijthe, Bouwe P</style></author><author><style face="normal" font="default" size="100%">Lyytikäinen, Leo-Pekka</style></author><author><style face="normal" font="default" size="100%">Müller, Christian</style></author><author><style face="normal" font="default" size="100%">Müller-Nurasyid, Martina</style></author><author><style face="normal" font="default" size="100%">Nolte, Ilja M</style></author><author><style face="normal" font="default" size="100%">Padmanabhan, Sandosh</style></author><author><style face="normal" font="default" size="100%">Ritchie, Marylyn D</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">Steri, Maristella</style></author><author><style face="normal" font="default" size="100%">Tanaka, Toshiko</style></author><author><style face="normal" font="default" size="100%">Teumer, Alexander</style></author><author><style face="normal" font="default" size="100%">Trompet, Stella</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">Verweij, Niek</style></author><author><style face="normal" font="default" size="100%">Yin, Xiaoyan</style></author><author><style face="normal" font="default" size="100%">Arnar, David O</style></author><author><style face="normal" font="default" size="100%">Asselbergs, Folkert W</style></author><author><style face="normal" font="default" size="100%">Bader, Joel S</style></author><author><style face="normal" font="default" size="100%">Barnard, John</style></author><author><style face="normal" font="default" size="100%">Bis, Josh</style></author><author><style face="normal" font="default" size="100%">Blankenberg, Stefan</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Bradford, Yuki</style></author><author><style face="normal" font="default" size="100%">Buckley, Brendan M</style></author><author><style face="normal" font="default" size="100%">Chung, Mina K</style></author><author><style face="normal" font="default" size="100%">Crawford, Dana</style></author><author><style face="normal" font="default" size="100%">den Hoed, Marcel</style></author><author><style face="normal" font="default" size="100%">Denny, Josh C</style></author><author><style face="normal" font="default" size="100%">Dominiczak, Anna F</style></author><author><style face="normal" font="default" size="100%">Ehret, Georg B</style></author><author><style face="normal" font="default" size="100%">Eijgelsheim, Mark</style></author><author><style face="normal" font="default" size="100%">Ellinor, Patrick T</style></author><author><style face="normal" font="default" size="100%">Felix, Stephan B</style></author><author><style face="normal" font="default" size="100%">Franco, Oscar 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face="normal" font="default" size="100%">Lin, Henry J</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Lubitz, Steven A</style></author><author><style face="normal" font="default" size="100%">Macfarlane, Peter W</style></author><author><style face="normal" font="default" size="100%">Magnani, Jared W</style></author><author><style face="normal" font="default" size="100%">Leach, Irene Mateo</style></author><author><style face="normal" font="default" size="100%">Meitinger, Thomas</style></author><author><style face="normal" font="default" size="100%">Mitchell, Braxton D</style></author><author><style face="normal" font="default" size="100%">Munzel, Thomas</style></author><author><style face="normal" font="default" size="100%">Papanicolaou, George J</style></author><author><style face="normal" font="default" size="100%">Peters, Annette</style></author><author><style face="normal" font="default" size="100%">Pfeufer, Arne</style></author><author><style face="normal" font="default" size="100%">Pramstaller, Peter P</style></author><author><style face="normal" font="default" size="100%">Raitakari, Olli T</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Samani, Nilesh J</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Silva Aldana, Claudia T</style></author><author><style face="normal" font="default" size="100%">Sinner, Moritz F</style></author><author><style face="normal" font="default" size="100%">Smith, Jonathan D</style></author><author><style face="normal" font="default" size="100%">Snieder, Harold</style></author><author><style face="normal" font="default" 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size="100%">Jan Westra, Harm</style></author><author><style face="normal" font="default" size="100%">Wild, Philipp S</style></author><author><style face="normal" font="default" size="100%">Zeller, Tanja</style></author><author><style face="normal" font="default" size="100%">Alonso, Alvaro</style></author><author><style face="normal" font="default" size="100%">Avery, Christy L</style></author><author><style face="normal" font="default" size="100%">Bandinelli, Stefania</style></author><author><style face="normal" font="default" size="100%">Benjamin, Emelia J</style></author><author><style face="normal" font="default" size="100%">Cucca, Francesco</style></author><author><style face="normal" font="default" size="100%">Dörr, Marcus</style></author><author><style face="normal" font="default" size="100%">Ferrucci, Luigi</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Heckbert, Susan R</style></author><author><style face="normal" font="default" size="100%">Hicks, Andrew A</style></author><author><style face="normal" font="default" size="100%">Jukema, J Wouter</style></author><author><style face="normal" font="default" size="100%">Kääb, Stefan</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho</style></author><author><style face="normal" font="default" size="100%">Liu, Yongmei</style></author><author><style face="normal" font="default" size="100%">Munroe, Patricia B</style></author><author><style face="normal" font="default" size="100%">Parsa, Afshin</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Psaty, Bruce M</style></author><author><style face="normal" font="default" size="100%">Roden, Dan M</style></author><author><style face="normal" font="default" size="100%">Schnabel, Renate B</style></author><author><style face="normal" font="default" size="100%">Sinagra, Gianfranco</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Stricker, Bruno H</style></author><author><style face="normal" font="default" size="100%">van der Harst, Pim</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Wilson, James F</style></author><author><style face="normal" font="default" size="100%">Gharib, Sina A</style></author><author><style face="normal" font="default" size="100%">de Bakker, Paul I W</style></author><author><style face="normal" font="default" size="100%">Isaacs, Aaron</style></author><author><style face="normal" font="default" size="100%">Arking, Dan E</style></author><author><style face="normal" font="default" size="100%">Sotoodehnia, Nona</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Commun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat Commun</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Atrial Function</style></keyword><keyword><style  face="normal" font="default" size="100%">Atrioventricular Node</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrocardiography</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrophysiological Phenomena</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Linkage Disequilibrium</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 07 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">2904</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/30046033?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Day, Felix R</style></author><author><style face="normal" font="default" size="100%">Thompson, Deborah J</style></author><author><style face="normal" font="default" size="100%">Helgason, Hannes</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">Finucane, Hilary</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Ruth, Katherine S</style></author><author><style face="normal" font="default" size="100%">Whalen, Sean</style></author><author><style face="normal" font="default" size="100%">Sarkar, Abhishek K</style></author><author><style face="normal" font="default" size="100%">Albrecht, Eva</style></author><author><style face="normal" font="default" size="100%">Altmaier, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Amini, Marzyeh</style></author><author><style face="normal" font="default" size="100%">Barbieri, Caterina M</style></author><author><style face="normal" font="default" size="100%">Boutin, Thibaud</style></author><author><style face="normal" font="default" size="100%">Campbell, Archie</style></author><author><style face="normal" font="default" size="100%">Demerath, Ellen</style></author><author><style face="normal" font="default" size="100%">Giri, Ayush</style></author><author><style face="normal" font="default" size="100%">He, Chunyan</style></author><author><style face="normal" font="default" size="100%">Hottenga, Jouke J</style></author><author><style face="normal" font="default" size="100%">Karlsson, Robert</style></author><author><style face="normal" font="default" size="100%">Kolcic, Ivana</style></author><author><style face="normal" font="default" size="100%">Loh, Po-Ru</style></author><author><style face="normal" font="default" size="100%">Lunetta, Kathryn L</style></author><author><style face="normal" font="default" size="100%">Mangino, Massimo</style></author><author><style face="normal" font="default" size="100%">Marco, Brumat</style></author><author><style face="normal" font="default" size="100%">McMahon, George</style></author><author><style face="normal" font="default" size="100%">Medland, Sarah E</style></author><author><style face="normal" font="default" size="100%">Nolte, Ilja M</style></author><author><style face="normal" font="default" size="100%">Noordam, Raymond</style></author><author><style face="normal" font="default" size="100%">Nutile, Teresa</style></author><author><style face="normal" font="default" size="100%">Paternoster, Lavinia</style></author><author><style face="normal" font="default" size="100%">Perjakova, Natalia</style></author><author><style face="normal" font="default" size="100%">Porcu, Eleonora</style></author><author><style face="normal" font="default" size="100%">Rose, Lynda M</style></author><author><style face="normal" font="default" size="100%">Schraut, Katharina E</style></author><author><style face="normal" font="default" size="100%">Segrè, Ayellet V</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">Stolk, Lisette</style></author><author><style face="normal" font="default" size="100%">Teumer, Alexander</style></author><author><style face="normal" font="default" size="100%">Andrulis, Irene L</style></author><author><style face="normal" font="default" size="100%">Bandinelli, Stefania</style></author><author><style face="normal" font="default" size="100%">Beckmann, Matthias W</style></author><author><style face="normal" font="default" size="100%">Benitez, Javier</style></author><author><style face="normal" font="default" size="100%">Bergmann, Sven</style></author><author><style face="normal" font="default" size="100%">Bochud, Murielle</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Bojesen, Stig E</style></author><author><style face="normal" font="default" size="100%">Bolla, Manjeet K</style></author><author><style face="normal" font="default" size="100%">Brand, Judith S</style></author><author><style face="normal" font="default" size="100%">Brauch, Hiltrud</style></author><author><style face="normal" font="default" size="100%">Brenner, Hermann</style></author><author><style face="normal" font="default" size="100%">Broer, Linda</style></author><author><style face="normal" font="default" size="100%">Brüning, Thomas</style></author><author><style face="normal" font="default" size="100%">Buring, Julie E</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Catamo, Eulalia</style></author><author><style face="normal" font="default" size="100%">Chanock, Stephen</style></author><author><style face="normal" font="default" size="100%">Chenevix-Trench, Georgia</style></author><author><style face="normal" font="default" size="100%">Corre, Tanguy</style></author><author><style face="normal" font="default" size="100%">Couch, Fergus J</style></author><author><style face="normal" font="default" size="100%">Cousminer, Diana L</style></author><author><style face="normal" font="default" size="100%">Cox, Angela</style></author><author><style face="normal" font="default" size="100%">Crisponi, Laura</style></author><author><style face="normal" font="default" size="100%">Czene, Kamila</style></author><author><style face="normal" font="default" size="100%">Davey Smith, George</style></author><author><style face="normal" font="default" size="100%">de Geus, Eco J C N</style></author><author><style face="normal" font="default" size="100%">de Mutsert, Renée</style></author><author><style face="normal" font="default" size="100%">De Vivo, Immaculata</style></author><author><style face="normal" font="default" size="100%">Dennis, Joe</style></author><author><style face="normal" font="default" size="100%">Devilee, Peter</style></author><author><style face="normal" font="default" size="100%">Dos-Santos-Silva, Isabel</style></author><author><style face="normal" font="default" size="100%">Dunning, Alison M</style></author><author><style face="normal" font="default" size="100%">Eriksson, Johan G</style></author><author><style face="normal" font="default" size="100%">Fasching, Peter A</style></author><author><style face="normal" font="default" size="100%">Fernández-Rhodes, Lindsay</style></author><author><style face="normal" font="default" size="100%">Ferrucci, Luigi</style></author><author><style face="normal" font="default" size="100%">Flesch-Janys, Dieter</style></author><author><style face="normal" font="default" size="100%">Franke, Lude</style></author><author><style face="normal" font="default" size="100%">Gabrielson, Marike</style></author><author><style face="normal" font="default" size="100%">Gandin, Ilaria</style></author><author><style face="normal" font="default" size="100%">Giles, Graham G</style></author><author><style face="normal" font="default" size="100%">Grallert, Harald</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Guenel, Pascal</style></author><author><style face="normal" font="default" size="100%">Hall, Per</style></author><author><style face="normal" font="default" size="100%">Hallberg, Emily</style></author><author><style face="normal" font="default" size="100%">Hamann, Ute</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hartman, Catharina A</style></author><author><style face="normal" font="default" size="100%">Heiss, Gerardo</style></author><author><style face="normal" font="default" size="100%">Hooning, Maartje J</style></author><author><style face="normal" font="default" size="100%">Hopper, John L</style></author><author><style face="normal" font="default" size="100%">Hu, Frank</style></author><author><style face="normal" font="default" size="100%">Hunter, David J</style></author><author><style 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font="default" size="100%">Laven, Joop S E</style></author><author><style face="normal" font="default" size="100%">Lenarduzzi, Stefania</style></author><author><style face="normal" font="default" size="100%">Li, Jingmei</style></author><author><style face="normal" font="default" size="100%">Lind, Penelope A</style></author><author><style face="normal" font="default" size="100%">Lindström, Sara</style></author><author><style face="normal" font="default" size="100%">Liu, Yongmei</style></author><author><style face="normal" font="default" size="100%">Luan, Jian'an</style></author><author><style face="normal" font="default" size="100%">Mägi, Reedik</style></author><author><style face="normal" font="default" size="100%">Mannermaa, Arto</style></author><author><style face="normal" font="default" size="100%">Mbarek, Hamdi</style></author><author><style face="normal" font="default" size="100%">McCarthy, Mark I</style></author><author><style face="normal" font="default" size="100%">Meisinger, Christa</style></author><author><style face="normal" font="default" size="100%">Meitinger, Thomas</style></author><author><style face="normal" font="default" size="100%">Menni, Cristina</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Michailidou, Kyriaki</style></author><author><style face="normal" font="default" size="100%">Milani, Lili</style></author><author><style face="normal" font="default" size="100%">Milne, Roger L</style></author><author><style face="normal" font="default" size="100%">Montgomery, Grant W</style></author><author><style face="normal" font="default" size="100%">Mulligan, Anna M</style></author><author><style face="normal" font="default" size="100%">Nalls, Mike A</style></author><author><style face="normal" font="default" size="100%">Navarro, Pau</style></author><author><style face="normal" font="default" size="100%">Nevanlinna, Heli</style></author><author><style face="normal" font="default" size="100%">Nyholt, Dale R</style></author><author><style face="normal" font="default" size="100%">Oldehinkel, Albertine J</style></author><author><style face="normal" font="default" size="100%">O'Mara, Tracy A</style></author><author><style face="normal" font="default" size="100%">Padmanabhan, Sandosh</style></author><author><style face="normal" font="default" size="100%">Palotie, Aarno</style></author><author><style face="normal" font="default" size="100%">Pedersen, Nancy</style></author><author><style face="normal" font="default" size="100%">Peters, Annette</style></author><author><style face="normal" font="default" size="100%">Peto, Julian</style></author><author><style face="normal" font="default" size="100%">Pharoah, Paul D P</style></author><author><style face="normal" font="default" size="100%">Pouta, Anneli</style></author><author><style face="normal" font="default" size="100%">Radice, Paolo</style></author><author><style face="normal" font="default" size="100%">Rahman, Iffat</style></author><author><style face="normal" font="default" size="100%">Ring, Susan M</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Rosendaal, Frits R</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Rueedi, Rico</style></author><author><style face="normal" font="default" size="100%">Ruggiero, Daniela</style></author><author><style face="normal" font="default" size="100%">Sala, Cinzia F</style></author><author><style face="normal" font="default" size="100%">Schmidt, Marjanka K</style></author><author><style face="normal" font="default" size="100%">Scott, Robert A</style></author><author><style face="normal" font="default" size="100%">Shah, Mitul</style></author><author><style 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font="default" size="100%">Tyrer, Jonathan P</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">Edwards, Digna R Velez</style></author><author><style face="normal" font="default" size="100%">Vitart, Veronique</style></author><author><style face="normal" font="default" size="100%">Völker, Uwe</style></author><author><style face="normal" font="default" size="100%">Vollenweider, Peter</style></author><author><style face="normal" font="default" size="100%">Wang, Qin</style></author><author><style face="normal" font="default" size="100%">Widen, Elisabeth</style></author><author><style face="normal" font="default" size="100%">van Dijk, Ko Willems</style></author><author><style face="normal" font="default" size="100%">Willemsen, Gonneke</style></author><author><style face="normal" font="default" size="100%">Winqvist, Robert</style></author><author><style face="normal" font="default" size="100%">Wolffenbuttel, Bruce H R</style></author><author><style face="normal" font="default" size="100%">Zhao, Jing Hua</style></author><author><style face="normal" font="default" size="100%">Zoledziewska, Magdalena</style></author><author><style face="normal" font="default" size="100%">Zygmunt, Marek</style></author><author><style face="normal" font="default" size="100%">Alizadeh, Behrooz Z</style></author><author><style face="normal" font="default" size="100%">Boomsma, Dorret I</style></author><author><style face="normal" font="default" size="100%">Ciullo, Marina</style></author><author><style face="normal" font="default" size="100%">Cucca, Francesco</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Franceschini, Nora</style></author><author><style face="normal" font="default" size="100%">Gieger, Christian</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Kraft, Peter</style></author><author><style face="normal" font="default" size="100%">Lawlor, Debbie A</style></author><author><style face="normal" font="default" size="100%">Magnusson, Patrik K E</style></author><author><style face="normal" font="default" size="100%">Martin, Nicholas G</style></author><author><style face="normal" font="default" size="100%">Mook-Kanamori, Dennis O</style></author><author><style face="normal" font="default" size="100%">Nohr, Ellen A</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Porteous, David</style></author><author><style face="normal" font="default" size="100%">Price, Alkes L</style></author><author><style face="normal" font="default" 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Cohort Study</style></author><author><style face="normal" font="default" size="100%">InterAct Consortium</style></author><author><style face="normal" font="default" size="100%">kConFab/AOCS Investigators</style></author><author><style face="normal" font="default" size="100%">Endometrial Cancer Association Consortium</style></author><author><style face="normal" font="default" size="100%">Ovarian Cancer Association Consortium</style></author><author><style face="normal" font="default" size="100%">PRACTICAL Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Age Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Mass Index</style></keyword><keyword><style  face="normal" font="default" size="100%">Databases, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Genomic Imprinting</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Intercellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Membrane Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Menarche</style></keyword><keyword><style  face="normal" font="default" size="100%">Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Puberty</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Ribonucleoproteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">49</style></volume><pages><style face="normal" font="default" size="100%">834-841</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P &lt; 5 × 10) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28436984?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Day, Felix R</style></author><author><style face="normal" font="default" size="100%">Ruth, Katherine S</style></author><author><style face="normal" font="default" size="100%">Thompson, Deborah J</style></author><author><style face="normal" font="default" size="100%">Lunetta, Kathryn L</style></author><author><style face="normal" font="default" size="100%">Pervjakova, Natalia</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">Stolk, Lisette</style></author><author><style face="normal" font="default" size="100%">Finucane, Hilary K</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Bulik-Sullivan, Brendan</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Johnson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Elks, Cathy E</style></author><author><style face="normal" font="default" size="100%">Franceschini, Nora</style></author><author><style face="normal" font="default" size="100%">He, Chunyan</style></author><author><style face="normal" font="default" size="100%">Altmaier, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Brody, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Franke, Lude L</style></author><author><style face="normal" font="default" size="100%">Huffman, Jennifer E</style></author><author><style face="normal" font="default" size="100%">Keller, Margaux F</style></author><author><style face="normal" font="default" size="100%">McArdle, Patrick F</style></author><author><style face="normal" font="default" size="100%">Nutile, Teresa</style></author><author><style face="normal" font="default" size="100%">Porcu, Eleonora</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Rose, Lynda M</style></author><author><style face="normal" font="default" size="100%">Schick, Ursula M</style></author><author><style face="normal" font="default" size="100%">Smith, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Teumer, 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M</style></author><author><style face="normal" font="default" size="100%">Perry, John R B</style></author><author><style face="normal" font="default" size="100%">Murray, Anna</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">PRACTICAL Consortium</style></author><author><style face="normal" font="default" size="100%">kConFab investigators</style></author><author><style face="normal" font="default" size="100%">AOCS Investigators</style></author><author><style face="normal" font="default" size="100%">Generation Scotland</style></author><author><style face="normal" font="default" size="100%">EPIC-InterAct Consortium</style></author><author><style face="normal" font="default" size="100%">LifeLines Cohort Study</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">47</style></volume><pages><style face="normal" font="default" size="100%">1294-303</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26414677?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Lunetta, Kathryn L</style></author><author><style face="normal" font="default" size="100%">Day, Felix R</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Ruth, Katherine S</style></author><author><style face="normal" font="default" size="100%">Tung, Joyce Y</style></author><author><style face="normal" font="default" size="100%">Hinds, David A</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Elks, Cathy E</style></author><author><style face="normal" font="default" size="100%">Altmaier, Elisabeth</style></author><author><style face="normal" font="default" size="100%">He, Chunyan</style></author><author><style face="normal" font="default" size="100%">Huffman, Jennifer E</style></author><author><style face="normal" font="default" size="100%">Mihailov, Evelin</style></author><author><style face="normal" font="default" size="100%">Porcu, Eleonora</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Rose, Lynda M</style></author><author><style face="normal" font="default" size="100%">Schick, Ursula M</style></author><author><style face="normal" font="default" size="100%">Stolk, Lisette</style></author><author><style face="normal" font="default" size="100%">Teumer, Alexander</style></author><author><style face="normal" font="default" size="100%">Thompson, Deborah J</style></author><author><style face="normal" font="default" size="100%">Traglia, Michela</style></author><author><style face="normal" font="default" size="100%">Wang, Carol A</style></author><author><style face="normal" font="default" size="100%">Yerges-Armstrong, Laura M</style></author><author><style face="normal" font="default" size="100%">Antoniou, Antonis C</style></author><author><style face="normal" font="default" size="100%">Barbieri, Caterina</style></author><author><style face="normal" font="default" size="100%">Coviello, Andrea D</style></author><author><style face="normal" font="default" size="100%">Cucca, Francesco</style></author><author><style face="normal" font="default" size="100%">Demerath, Ellen W</style></author><author><style face="normal" font="default" size="100%">Dunning, Alison M</style></author><author><style face="normal" font="default" size="100%">Gandin, Ilaria</style></author><author><style face="normal" font="default" size="100%">Grove, Megan L</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Hocking, Lynne J</style></author><author><style face="normal" font="default" size="100%">Hofman, Albert</style></author><author><style face="normal" font="default" size="100%">Huang, Jinyan</style></author><author><style face="normal" font="default" size="100%">Jackson, Rebecca D</style></author><author><style face="normal" font="default" size="100%">Karasik, David</style></author><author><style face="normal" font="default" size="100%">Kriebel, Jennifer</style></author><author><style face="normal" font="default" size="100%">Lange, Ethan M</style></author><author><style face="normal" font="default" size="100%">Lange, Leslie A</style></author><author><style face="normal" font="default" size="100%">Langenberg, Claudia</style></author><author><style face="normal" font="default" size="100%">Li, Xin</style></author><author><style face="normal" font="default" size="100%">Luan, Jian'an</style></author><author><style face="normal" font="default" size="100%">Mägi, Reedik</style></author><author><style face="normal" font="default" size="100%">Morrison, Alanna C</style></author><author><style face="normal" font="default" size="100%">Padmanabhan, Sandosh</style></author><author><style face="normal" font="default" size="100%">Pirie, Ailith</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Porteous, David</style></author><author><style face="normal" font="default" size="100%">Reiner, Alex P</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Sala, Cinzia F</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Scott, Robert A</style></author><author><style face="normal" font="default" size="100%">Stöckl, Doris</style></author><author><style face="normal" font="default" size="100%">Visser, Jenny A</style></author><author><style face="normal" font="default" size="100%">Völker, Uwe</style></author><author><style face="normal" font="default" size="100%">Vozzi, Diego</style></author><author><style face="normal" font="default" size="100%">Wilson, James G</style></author><author><style face="normal" font="default" size="100%">Zygmunt, Marek</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Buring, Julie E</style></author><author><style face="normal" font="default" size="100%">Crisponi, Laura</style></author><author><style face="normal" font="default" size="100%">Easton, Douglas F</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Hu, Frank B</style></author><author><style face="normal" font="default" size="100%">Liu, Simin</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Pennell, Craig E</style></author><author><style face="normal" font="default" size="100%">Ridker, Paul M</style></author><author><style face="normal" font="default" size="100%">Strauch, Konstantin</style></author><author><style face="normal" font="default" size="100%">Streeten, Elizabeth A</style></author><author><style face="normal" font="default" size="100%">Toniolo, Daniela</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">Völzke, Henry</style></author><author><style face="normal" font="default" size="100%">Wareham, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Wellons, Melissa</style></author><author><style face="normal" font="default" size="100%">Franceschini, Nora</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Murray, Anna</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Murabito, Joanne M</style></author><author><style face="normal" font="default" size="100%">Ong, Ken K</style></author><author><style face="normal" font="default" size="100%">Perry, John R B</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">EPIC-InterAct Consortium</style></author><author><style face="normal" font="default" size="100%">Generation Scotland</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Rare coding variants and X-linked loci associated with age at menarche.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Commun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat Commun</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">7756</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P&lt;5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26239645?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Arking, Dan E</style></author><author><style face="normal" font="default" size="100%">Pulit, Sara L</style></author><author><style face="normal" font="default" size="100%">Crotti, Lia</style></author><author><style face="normal" font="default" size="100%">van der Harst, Pim</style></author><author><style face="normal" font="default" size="100%">Munroe, Patricia B</style></author><author><style face="normal" font="default" size="100%">Koopmann, Tamara T</style></author><author><style face="normal" font="default" size="100%">Sotoodehnia, Nona</style></author><author><style face="normal" font="default" size="100%">Rossin, Elizabeth J</style></author><author><style face="normal" font="default" size="100%">Morley, Michael</style></author><author><style face="normal" font="default" size="100%">Wang, Xinchen</style></author><author><style face="normal" font="default" size="100%">Johnson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Lundby, Alicia</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Noseworthy, Peter A</style></author><author><style face="normal" font="default" size="100%">Eijgelsheim, Mark</style></author><author><style face="normal" font="default" size="100%">Bradford, Yuki</style></author><author><style face="normal" font="default" size="100%">Tarasov, Kirill V</style></author><author><style face="normal" font="default" size="100%">Dörr, Marcus</style></author><author><style face="normal" font="default" size="100%">Müller-Nurasyid, Martina</style></author><author><style face="normal" font="default" size="100%">Lahtinen, Annukka M</style></author><author><style face="normal" font="default" size="100%">Nolte, Ilja M</style></author><author><style face="normal" font="default" size="100%">Smith, Albert Vernon</style></author><author><style face="normal" font="default" size="100%">Bis, Joshua C</style></author><author><style face="normal" font="default" size="100%">Isaacs, Aaron</style></author><author><style face="normal" font="default" size="100%">Newhouse, Stephen J</style></author><author><style face="normal" font="default" size="100%">Evans, Daniel S</style></author><author><style face="normal" font="default" size="100%">Post, Wendy S</style></author><author><style face="normal" font="default" size="100%">Waggott, Daryl</style></author><author><style face="normal" font="default" size="100%">Lyytikäinen, Leo-Pekka</style></author><author><style face="normal" font="default" size="100%">Hicks, Andrew A</style></author><author><style face="normal" font="default" size="100%">Eisele, Lewin</style></author><author><style face="normal" font="default" size="100%">Ellinghaus, David</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Navarro, Pau</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">Tanaka, Toshiko</style></author><author><style face="normal" font="default" size="100%">Tester, David J</style></author><author><style face="normal" font="default" size="100%">Chatel, Stéphanie</style></author><author><style face="normal" font="default" size="100%">Gustafsson, Stefan</style></author><author><style face="normal" font="default" size="100%">Kumari, Meena</style></author><author><style face="normal" font="default" size="100%">Morris, Richard W</style></author><author><style face="normal" font="default" size="100%">Naluai, Åsa T</style></author><author><style face="normal" font="default" size="100%">Padmanabhan, Sandosh</style></author><author><style face="normal" font="default" size="100%">Kluttig, Alexander</style></author><author><style face="normal" font="default" size="100%">Strohmer, Bernhard</style></author><author><style face="normal" font="default" size="100%">Panayiotou, Andrie G</style></author><author><style face="normal" font="default" size="100%">Torres, Maria</style></author><author><style face="normal" font="default" size="100%">Knoflach, Michael</style></author><author><style face="normal" font="default" size="100%">Hubacek, Jaroslav A</style></author><author><style face="normal" font="default" size="100%">Slowikowski, Kamil</style></author><author><style face="normal" font="default" size="100%">Raychaudhuri, Soumya</style></author><author><style face="normal" font="default" size="100%">Kumar, Runjun D</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Launer, Lenore J</style></author><author><style face="normal" font="default" size="100%">Shuldiner, Alan R</style></author><author><style face="normal" font="default" size="100%">Alonso, Alvaro</style></author><author><style face="normal" font="default" size="100%">Bader, Joel S</style></author><author><style face="normal" font="default" size="100%">Ehret, Georg</style></author><author><style face="normal" font="default" size="100%">Huang, Hailiang</style></author><author><style face="normal" font="default" size="100%">Kao, W H Linda</style></author><author><style face="normal" font="default" size="100%">Strait, James B</style></author><author><style face="normal" font="default" size="100%">Macfarlane, Peter W</style></author><author><style face="normal" font="default" size="100%">Brown, Morris</style></author><author><style face="normal" font="default" size="100%">Caulfield, Mark J</style></author><author><style face="normal" font="default" size="100%">Samani, Nilesh J</style></author><author><style face="normal" font="default" size="100%">Kronenberg, Florian</style></author><author><style face="normal" font="default" size="100%">Willeit, Johann</style></author><author><style face="normal" font="default" size="100%">Smith, J Gustav</style></author><author><style face="normal" font="default" size="100%">Greiser, Karin H</style></author><author><style face="normal" font="default" size="100%">Meyer Zu Schwabedissen, Henriette</style></author><author><style face="normal" font="default" size="100%">Werdan, Karl</style></author><author><style face="normal" font="default" size="100%">Carella, Massimo</style></author><author><style face="normal" font="default" size="100%">Zelante, Leopoldo</style></author><author><style face="normal" font="default" size="100%">Heckbert, Susan R</style></author><author><style face="normal" font="default" size="100%">Psaty, Bruce M</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Kolcic, Ivana</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Wright, Alan F</style></author><author><style face="normal" font="default" size="100%">Griffin, Maura</style></author><author><style face="normal" font="default" size="100%">Daly, Mark J</style></author><author><style face="normal" font="default" size="100%">Arnar, David O</style></author><author><style face="normal" font="default" size="100%">Holm, Hilma</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Denny, Joshua C</style></author><author><style face="normal" font="default" size="100%">Roden, Dan M</style></author><author><style face="normal" font="default" size="100%">Zuvich, Rebecca L</style></author><author><style face="normal" font="default" size="100%">Emilsson, Valur</style></author><author><style face="normal" font="default" size="100%">Plump, Andrew S</style></author><author><style face="normal" font="default" size="100%">Larson, Martin G</style></author><author><style face="normal" font="default" size="100%">O'Donnell, Christopher J</style></author><author><style face="normal" font="default" size="100%">Yin, Xiaoyan</style></author><author><style face="normal" font="default" size="100%">Bobbo, Marco</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Adamo P</style></author><author><style face="normal" font="default" size="100%">Iorio, Annamaria</style></author><author><style face="normal" font="default" size="100%">Sinagra, Gianfranco</style></author><author><style face="normal" font="default" size="100%">Carracedo, Angel</style></author><author><style face="normal" font="default" size="100%">Cummings, Steven R</style></author><author><style face="normal" font="default" size="100%">Nalls, Michael A</style></author><author><style face="normal" font="default" size="100%">Jula, Antti</style></author><author><style face="normal" font="default" size="100%">Kontula, Kimmo K</style></author><author><style face="normal" font="default" size="100%">Marjamaa, Annukka</style></author><author><style face="normal" font="default" size="100%">Oikarinen, Lasse</style></author><author><style face="normal" font="default" size="100%">Perola, Markus</style></author><author><style face="normal" font="default" size="100%">Porthan, Kimmo</style></author><author><style face="normal" font="default" size="100%">Erbel, Raimund</style></author><author><style face="normal" font="default" size="100%">Hoffmann, Per</style></author><author><style face="normal" font="default" size="100%">Jöckel, Karl-Heinz</style></author><author><style face="normal" font="default" size="100%">Kälsch, Hagen</style></author><author><style face="normal" font="default" size="100%">Nöthen, Markus M</style></author><author><style face="normal" font="default" size="100%">den Hoed, Marcel</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Thelle, Dag S</style></author><author><style face="normal" font="default" size="100%">Gieger, Christian</style></author><author><style face="normal" font="default" size="100%">Meitinger, Thomas</style></author><author><style face="normal" font="default" size="100%">Perz, Siegfried</style></author><author><style face="normal" font="default" size="100%">Peters, Annette</style></author><author><style face="normal" font="default" size="100%">Prucha, Hanna</style></author><author><style face="normal" font="default" size="100%">Sinner, Moritz F</style></author><author><style face="normal" font="default" size="100%">Waldenberger, Melanie</style></author><author><style face="normal" font="default" size="100%">de Boer, Rudolf A</style></author><author><style face="normal" font="default" size="100%">Franke, Lude</style></author><author><style face="normal" font="default" size="100%">van der Vleuten, Pieter A</style></author><author><style face="normal" font="default" size="100%">Beckmann, Britt Maria</style></author><author><style face="normal" font="default" size="100%">Martens, Eimo</style></author><author><style face="normal" font="default" size="100%">Bardai, Abdennasser</style></author><author><style face="normal" font="default" size="100%">Hofman, Nynke</style></author><author><style face="normal" font="default" size="100%">Wilde, Arthur A M</style></author><author><style face="normal" font="default" size="100%">Behr, Elijah R</style></author><author><style face="normal" font="default" size="100%">Dalageorgou, Chrysoula</style></author><author><style face="normal" font="default" size="100%">Giudicessi, John R</style></author><author><style face="normal" font="default" size="100%">Medeiros-Domingo, Argelia</style></author><author><style face="normal" font="default" size="100%">Barc, Julien</style></author><author><style face="normal" font="default" size="100%">Kyndt, Florence</style></author><author><style face="normal" font="default" size="100%">Probst, Vincent</style></author><author><style face="normal" font="default" size="100%">Ghidoni, Alice</style></author><author><style face="normal" font="default" size="100%">Insolia, Roberto</style></author><author><style face="normal" font="default" size="100%">Hamilton, Robert M</style></author><author><style face="normal" font="default" size="100%">Scherer, Stephen W</style></author><author><style face="normal" font="default" size="100%">Brandimarto, Jeffrey</style></author><author><style face="normal" font="default" size="100%">Margulies, Kenneth</style></author><author><style face="normal" font="default" size="100%">Moravec, Christine E</style></author><author><style face="normal" font="default" size="100%">del Greco M, Fabiola</style></author><author><style face="normal" font="default" size="100%">Fuchsberger, Christian</style></author><author><style face="normal" font="default" size="100%">O'Connell, Jeffrey R</style></author><author><style face="normal" font="default" size="100%">Lee, Wai K</style></author><author><style face="normal" font="default" size="100%">Watt, Graham C M</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Wild, Sarah H</style></author><author><style face="normal" font="default" size="100%">El Mokhtari, Nour 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A</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">Witteman, Jacqueline C M</style></author><author><style face="normal" font="default" size="100%">Kedenko, Lyudmyla</style></author><author><style face="normal" font="default" size="100%">Lamina, Claudia</style></author><author><style face="normal" font="default" size="100%">Oostra, Ben A</style></author><author><style face="normal" font="default" size="100%">Abecasis, Goncalo R</style></author><author><style face="normal" font="default" size="100%">Lakatta, Edward G</style></author><author><style face="normal" font="default" size="100%">Mulas, Antonella</style></author><author><style face="normal" font="default" size="100%">Orru, Marco</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Uda, Manuela</style></author><author><style face="normal" font="default" size="100%">Markus, Marcello R P</style></author><author><style face="normal" font="default" size="100%">Völker, Uwe</style></author><author><style face="normal" font="default" size="100%">Snieder, Harold</style></author><author><style face="normal" font="default" size="100%">Spector, Timothy D</style></author><author><style face="normal" font="default" size="100%">Arnlöv, Johan</style></author><author><style face="normal" font="default" size="100%">Lind, Lars</style></author><author><style face="normal" font="default" size="100%">Sundström, Johan</style></author><author><style face="normal" font="default" size="100%">Syvänen, Ann-Christine</style></author><author><style face="normal" font="default" size="100%">Kivimaki, Mika</style></author><author><style face="normal" font="default" size="100%">Kähönen, Mika</style></author><author><style face="normal" font="default" size="100%">Mononen, Nina</style></author><author><style face="normal" font="default" size="100%">Raitakari, Olli T</style></author><author><style face="normal" font="default" size="100%">Viikari, Jorma S</style></author><author><style face="normal" font="default" size="100%">Adamkova, Vera</style></author><author><style face="normal" font="default" size="100%">Kiechl, Stefan</style></author><author><style face="normal" font="default" size="100%">Brion, Maria</style></author><author><style face="normal" font="default" size="100%">Nicolaides, Andrew N</style></author><author><style face="normal" font="default" size="100%">Paulweber, Bernhard</style></author><author><style face="normal" font="default" size="100%">Haerting, Johannes</style></author><author><style face="normal" font="default" size="100%">Dominiczak, Anna F</style></author><author><style face="normal" font="default" size="100%">Nyberg, Fredrik</style></author><author><style face="normal" font="default" size="100%">Whincup, Peter H</style></author><author><style face="normal" font="default" size="100%">Hingorani, Aroon D</style></author><author><style face="normal" font="default" size="100%">Schott, Jean-Jacques</style></author><author><style face="normal" font="default" size="100%">Bezzina, Connie R</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Ferrucci, Luigi</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Wilson, James F</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Franke, Andre</style></author><author><style face="normal" font="default" size="100%">Mühleisen, Thomas W</style></author><author><style face="normal" font="default" size="100%">Pramstaller, Peter P</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho J</style></author><author><style face="normal" font="default" size="100%">Paterson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Parsa, Afshin</style></author><author><style face="normal" font="default" size="100%">Liu, Yongmei</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Siscovick, David S</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Jamshidi, Yalda</style></author><author><style face="normal" font="default" size="100%">Salomaa, Veikko</style></author><author><style face="normal" font="default" size="100%">Felix, Stephan B</style></author><author><style face="normal" font="default" size="100%">Sanna, Serena</style></author><author><style face="normal" font="default" size="100%">Ritchie, Marylyn D</style></author><author><style face="normal" font="default" size="100%">Stricker, Bruno H</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Boyer, Laurie A</style></author><author><style face="normal" font="default" size="100%">Cappola, Thomas P</style></author><author><style face="normal" font="default" size="100%">Olsen, Jesper V</style></author><author><style face="normal" font="default" size="100%">Lage, Kasper</style></author><author><style face="normal" font="default" size="100%">Schwartz, Peter J</style></author><author><style face="normal" font="default" size="100%">Kääb, Stefan</style></author><author><style face="normal" font="default" size="100%">Chakravarti, Aravinda</style></author><author><style face="normal" font="default" size="100%">Ackerman, Michael J</style></author><author><style face="normal" font="default" size="100%">Pfeufer, Arne</style></author><author><style face="normal" font="default" size="100%">de Bakker, Paul I W</style></author><author><style face="normal" font="default" size="100%">Newton-Cheh, Christopher</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">CARe Consortium</style></author><author><style face="normal" font="default" size="100%">COGENT Consortium</style></author><author><style face="normal" font="default" size="100%">DCCT/EDIC</style></author><author><style face="normal" font="default" size="100%">eMERGE Consortium</style></author><author><style face="normal" font="default" size="100%">HRGEN Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Arrhythmias, Cardiac</style></keyword><keyword><style  face="normal" font="default" size="100%">Calcium Signaling</style></keyword><keyword><style  face="normal" font="default" size="100%">Death, Sudden, Cardiac</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrocardiography</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Ventricles</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Long QT Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardium</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">46</style></volume><pages><style face="normal" font="default" size="100%">826-36</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24952745?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Perry, John R B</style></author><author><style face="normal" font="default" size="100%">Day, Felix</style></author><author><style face="normal" font="default" size="100%">Elks, Cathy E</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" 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font="default" size="100%">Mihailov, Evelin</style></author><author><style face="normal" font="default" size="100%">Milani, Lili</style></author><author><style face="normal" font="default" size="100%">Milne, Roger L</style></author><author><style face="normal" font="default" size="100%">Nevanlinna, Heli</style></author><author><style face="normal" font="default" size="100%">Neven, Patrick</style></author><author><style face="normal" font="default" size="100%">Nohr, Ellen A</style></author><author><style face="normal" font="default" size="100%">Oldehinkel, Albertine J</style></author><author><style face="normal" font="default" size="100%">Oostra, Ben A</style></author><author><style face="normal" font="default" size="100%">Palotie, Aarno</style></author><author><style face="normal" font="default" size="100%">Peacock, Munro</style></author><author><style face="normal" font="default" size="100%">Pedersen, Nancy L</style></author><author><style face="normal" font="default" size="100%">Peterlongo, Paolo</style></author><author><style face="normal" font="default" size="100%">Peto, Julian</style></author><author><style face="normal" font="default" size="100%">Pharoah, Paul D P</style></author><author><style face="normal" font="default" size="100%">Postma, Dirkje S</style></author><author><style face="normal" font="default" size="100%">Pouta, Anneli</style></author><author><style face="normal" font="default" size="100%">Pylkäs, Katri</style></author><author><style face="normal" font="default" size="100%">Radice, Paolo</style></author><author><style face="normal" font="default" size="100%">Ring, Susan</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Rose, Lynda M</style></author><author><style face="normal" font="default" size="100%">Rudolph, Anja</style></author><author><style face="normal" font="default" size="100%">Salomaa, Veikko</style></author><author><style face="normal" font="default" size="100%">Sanna, Serena</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Schmidt, Marjanka K</style></author><author><style face="normal" font="default" size="100%">Southey, Mellissa C</style></author><author><style face="normal" font="default" size="100%">Sovio, Ulla</style></author><author><style face="normal" font="default" size="100%">Stampfer, Meir J</style></author><author><style face="normal" font="default" size="100%">Stöckl, Doris</style></author><author><style face="normal" font="default" size="100%">Storniolo, Anna M</style></author><author><style face="normal" font="default" size="100%">Timpson, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Tyrer, Jonathan</style></author><author><style face="normal" font="default" size="100%">Visser, Jenny A</style></author><author><style face="normal" font="default" size="100%">Vollenweider, Peter</style></author><author><style face="normal" font="default" size="100%">Völzke, Henry</style></author><author><style face="normal" font="default" size="100%">Waeber, Gerard</style></author><author><style face="normal" font="default" size="100%">Waldenberger, Melanie</style></author><author><style face="normal" font="default" size="100%">Wallaschofski, Henri</style></author><author><style face="normal" font="default" size="100%">Wang, Qin</style></author><author><style face="normal" font="default" size="100%">Willemsen, Gonneke</style></author><author><style face="normal" font="default" size="100%">Winqvist, Robert</style></author><author><style face="normal" font="default" size="100%">Wolffenbuttel, Bruce H R</style></author><author><style face="normal" font="default" size="100%">Wright, Margaret J</style></author><author><style face="normal" font="default" size="100%">Boomsma, Dorret I</style></author><author><style face="normal" font="default" size="100%">Econs, Michael J</style></author><author><style face="normal" font="default" size="100%">Khaw, Kay-Tee</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">McCarthy, Mark I</style></author><author><style face="normal" font="default" size="100%">Montgomery, Grant W</style></author><author><style face="normal" font="default" size="100%">Rice, John P</style></author><author><style face="normal" font="default" size="100%">Streeten, Elizabeth A</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Alizadeh, Behrooz Z</style></author><author><style face="normal" font="default" size="100%">Bergmann, Sven</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Boyd, Heather A</style></author><author><style face="normal" font="default" size="100%">Crisponi, Laura</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Gieger, Christian</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Järvelin, Marjo-Riitta</style></author><author><style face="normal" font="default" size="100%">Kraft, Peter</style></author><author><style face="normal" font="default" size="100%">Lawlor, Debbie</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Pennell, Craig E</style></author><author><style face="normal" font="default" size="100%">Ridker, Paul M</style></author><author><style face="normal" font="default" size="100%">Snieder, Harold</style></author><author><style face="normal" font="default" size="100%">Sørensen, Thorkild I A</style></author><author><style face="normal" font="default" size="100%">Spector, Tim D</style></author><author><style face="normal" font="default" size="100%">Strachan, David P</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">Wareham, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Widen, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Zygmunt, Marek</style></author><author><style face="normal" font="default" size="100%">Murray, Anna</style></author><author><style face="normal" font="default" size="100%">Easton, Douglas F</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Murabito, Joanne M</style></author><author><style face="normal" font="default" size="100%">Ong, Ken K</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">Australian Ovarian Cancer Study</style></author><author><style face="normal" font="default" size="100%">GENICA Network</style></author><author><style face="normal" font="default" size="100%">kConFab</style></author><author><style face="normal" font="default" size="100%">LifeLines Cohort Study</style></author><author><style face="normal" font="default" size="100%">InterAct Consortium</style></author><author><style face="normal" font="default" size="100%">Early Growth Genetics (EGG) Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.</style></title><secondary-title><style face="normal" font="default" size="100%">Nature</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nature</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Age Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Mass Index</style></keyword><keyword><style  face="normal" font="default" size="100%">Breast Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiovascular Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Type 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Europe</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Genomic Imprinting</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypothalamo-Hypophyseal System</style></keyword><keyword><style  face="normal" font="default" size="100%">Intercellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Membrane Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Menarche</style></keyword><keyword><style  face="normal" font="default" size="100%">Obesity</style></keyword><keyword><style  face="normal" font="default" size="100%">Ovary</style></keyword><keyword><style  face="normal" font="default" size="100%">Parents</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Potassium Channels, Tandem Pore Domain</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, GABA-B</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Retinoic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Ribonucleoproteins</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Oct 2</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">514</style></volume><pages><style face="normal" font="default" size="100%">92-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P &lt; 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7520</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/25231870?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stolk, Lisette</style></author><author><style face="normal" font="default" size="100%">Perry, John R B</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">He, Chunyan</style></author><author><style face="normal" font="default" size="100%">Mangino, Massimo</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Barbalic, Maja</style></author><author><style face="normal" font="default" size="100%">Broer, Linda</style></author><author><style face="normal" font="default" size="100%">Byrne, Enda M</style></author><author><style face="normal" font="default" size="100%">Ernst, Florian</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Franceschini, Nora</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Hottenga, Jouke-Jan</style></author><author><style face="normal" font="default" size="100%">Kraft, Peter</style></author><author><style face="normal" font="default" size="100%">McArdle, Patrick F</style></author><author><style face="normal" font="default" size="100%">Porcu, Eleonora</style></author><author><style face="normal" font="default" size="100%">Shin, So-Youn</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">van Wingerden, Sophie</style></author><author><style face="normal" font="default" size="100%">Zhai, Guangju</style></author><author><style face="normal" font="default" size="100%">Zhuang, Wei V</style></author><author><style face="normal" font="default" size="100%">Albrecht, Eva</style></author><author><style face="normal" font="default" size="100%">Alizadeh, Behrooz Z</style></author><author><style face="normal" font="default" size="100%">Aspelund, Thor</style></author><author><style face="normal" font="default" size="100%">Bandinelli, Stefania</style></author><author><style face="normal" font="default" size="100%">Lauc, Lovorka Barac</style></author><author><style face="normal" font="default" size="100%">Beckmann, Jacques S</style></author><author><style face="normal" font="default" size="100%">Boban, Mladen</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Broekmans, Frank J</style></author><author><style face="normal" font="default" size="100%">Burri, Andrea</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Chanock, Stephen J</style></author><author><style face="normal" font="default" size="100%">Chen, Constance</style></author><author><style face="normal" font="default" size="100%">Cornelis, Marilyn C</style></author><author><style face="normal" font="default" size="100%">Corre, Tanguy</style></author><author><style face="normal" font="default" size="100%">Coviello, Andrea D</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">Davies, Gail</style></author><author><style face="normal" font="default" size="100%">de Faire, Ulf</style></author><author><style face="normal" font="default" size="100%">de Geus, Eco J C</style></author><author><style face="normal" font="default" size="100%">Deary, Ian J</style></author><author><style face="normal" font="default" size="100%">Dedoussis, George V Z</style></author><author><style face="normal" font="default" size="100%">Deloukas, Panagiotis</style></author><author><style face="normal" font="default" size="100%">Ebrahim, Shah</style></author><author><style face="normal" font="default" size="100%">Eiriksdottir, Gudny</style></author><author><style face="normal" font="default" size="100%">Emilsson, Valur</style></author><author><style face="normal" font="default" size="100%">Eriksson, Johan G</style></author><author><style face="normal" font="default" size="100%">Fauser, Bart C J M</style></author><author><style face="normal" font="default" size="100%">Ferreli, Liana</style></author><author><style face="normal" font="default" size="100%">Ferrucci, Luigi</style></author><author><style face="normal" font="default" size="100%">Fischer, Krista</style></author><author><style face="normal" font="default" size="100%">Folsom, Aaron R</style></author><author><style face="normal" font="default" size="100%">Garcia, Melissa E</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Gieger, Christian</style></author><author><style face="normal" font="default" size="100%">Glazer, Nicole</style></author><author><style face="normal" font="default" size="100%">Grobbee, Diederick E</style></author><author><style face="normal" font="default" size="100%">Hall, Per</style></author><author><style face="normal" font="default" size="100%">Haller, Toomas</style></author><author><style face="normal" font="default" size="100%">Hankinson, Susan E</style></author><author><style face="normal" font="default" size="100%">Hass, Merli</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Heath, Andrew C</style></author><author><style face="normal" font="default" size="100%">Hofman, Albert</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Janssens, A Cecile J W</style></author><author><style face="normal" font="default" size="100%">Johnson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Karasik, David</style></author><author><style face="normal" font="default" size="100%">Kardia, Sharon L R</style></author><author><style face="normal" font="default" size="100%">Keyzer, Jules</style></author><author><style face="normal" font="default" size="100%">Kiel, Douglas P</style></author><author><style face="normal" font="default" size="100%">Kolcic, Ivana</style></author><author><style face="normal" font="default" size="100%">Kutalik, Zoltán</style></author><author><style face="normal" font="default" size="100%">Lahti, Jari</style></author><author><style face="normal" font="default" size="100%">Lai, Sandra</style></author><author><style face="normal" font="default" size="100%">Laisk, Triin</style></author><author><style face="normal" font="default" size="100%">Laven, Joop S E</style></author><author><style face="normal" font="default" size="100%">Lawlor, Debbie A</style></author><author><style face="normal" font="default" size="100%">Liu, Jianjun</style></author><author><style face="normal" font="default" size="100%">Lopez, Lorna M</style></author><author><style face="normal" font="default" size="100%">Louwers, Yvonne V</style></author><author><style face="normal" font="default" size="100%">Magnusson, Patrik K E</style></author><author><style face="normal" font="default" size="100%">Marongiu, Mara</style></author><author><style face="normal" font="default" size="100%">Martin, Nicholas G</style></author><author><style face="normal" font="default" size="100%">Klaric, Irena Martinovic</style></author><author><style face="normal" font="default" size="100%">Masciullo, Corrado</style></author><author><style face="normal" font="default" size="100%">McKnight, Barbara</style></author><author><style face="normal" font="default" size="100%">Medland, Sarah E</style></author><author><style face="normal" font="default" size="100%">Melzer, David</style></author><author><style face="normal" font="default" size="100%">Mooser, Vincent</style></author><author><style face="normal" font="default" size="100%">Navarro, Pau</style></author><author><style face="normal" font="default" size="100%">Newman, Anne B</style></author><author><style face="normal" font="default" size="100%">Nyholt, Dale R</style></author><author><style face="normal" font="default" size="100%">Onland-Moret, N Charlotte</style></author><author><style face="normal" font="default" size="100%">Palotie, Aarno</style></author><author><style face="normal" font="default" size="100%">Paré, Guillaume</style></author><author><style face="normal" font="default" size="100%">Parker, Alex N</style></author><author><style face="normal" font="default" size="100%">Pedersen, Nancy L</style></author><author><style face="normal" font="default" size="100%">Peeters, Petra H M</style></author><author><style face="normal" font="default" size="100%">Pistis, Giorgio</style></author><author><style face="normal" font="default" size="100%">Plump, Andrew S</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Pop, Victor J M</style></author><author><style face="normal" font="default" size="100%">Psaty, Bruce M</style></author><author><style face="normal" font="default" size="100%">Räikkönen, Katri</style></author><author><style face="normal" font="default" size="100%">Rehnberg, Emil</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Sala, Cinzia</style></author><author><style face="normal" font="default" size="100%">Salumets, Andres</style></author><author><style face="normal" font="default" size="100%">Scuteri, Angelo</style></author><author><style face="normal" font="default" size="100%">Singleton, Andrew</style></author><author><style face="normal" font="default" size="100%">Smith, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Snieder, Harold</style></author><author><style face="normal" font="default" size="100%">Soranzo, Nicole</style></author><author><style face="normal" font="default" size="100%">Stacey, Simon N</style></author><author><style face="normal" font="default" size="100%">Starr, John M</style></author><author><style face="normal" font="default" size="100%">Stathopoulou, Maria G</style></author><author><style face="normal" font="default" size="100%">Stirrups, Kathleen</style></author><author><style face="normal" font="default" size="100%">Stolk, Ronald P</style></author><author><style face="normal" font="default" size="100%">Styrkarsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Sun, Yan V</style></author><author><style face="normal" font="default" size="100%">Tenesa, Albert</style></author><author><style face="normal" font="default" size="100%">Thorand, Barbara</style></author><author><style face="normal" font="default" size="100%">Toniolo, Daniela</style></author><author><style face="normal" font="default" size="100%">Tryggvadottir, Laufey</style></author><author><style face="normal" font="default" size="100%">Tsui, Kim</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">van Dam, Rob M</style></author><author><style face="normal" font="default" size="100%">van der Schouw, Yvonne T</style></author><author><style face="normal" font="default" size="100%">van Gils, Carla H</style></author><author><style face="normal" font="default" size="100%">van Nierop, Peter</style></author><author><style face="normal" font="default" size="100%">Vink, Jacqueline M</style></author><author><style face="normal" font="default" size="100%">Visscher, Peter M</style></author><author><style face="normal" font="default" size="100%">Voorhuis, Marlies</style></author><author><style face="normal" font="default" size="100%">Waeber, Gerard</style></author><author><style face="normal" font="default" size="100%">Wallaschofski, Henri</style></author><author><style face="normal" font="default" size="100%">Wichmann, H Erich</style></author><author><style face="normal" font="default" size="100%">Widen, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Wijnands-van Gent, Colette J M</style></author><author><style face="normal" font="default" size="100%">Willemsen, Gonneke</style></author><author><style face="normal" font="default" size="100%">Wilson, James F</style></author><author><style face="normal" font="default" size="100%">Wolffenbuttel, Bruce H R</style></author><author><style face="normal" font="default" size="100%">Wright, Alan F</style></author><author><style face="normal" font="default" size="100%">Yerges-Armstrong, Laura M</style></author><author><style face="normal" font="default" size="100%">Zemunik, Tatijana</style></author><author><style face="normal" font="default" size="100%">Zgaga, Lina</style></author><author><style face="normal" font="default" size="100%">Zillikens, M Carola</style></author><author><style face="normal" font="default" size="100%">Zygmunt, Marek</style></author><author><style face="normal" font="default" size="100%">Arnold, Alice M</style></author><author><style face="normal" font="default" size="100%">Boomsma, Dorret I</style></author><author><style face="normal" font="default" size="100%">Buring, Julie E</style></author><author><style face="normal" font="default" size="100%">Crisponi, Laura</style></author><author><style face="normal" font="default" size="100%">Demerath, Ellen W</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hu, Frank B</style></author><author><style face="normal" font="default" size="100%">Hunter, David J</style></author><author><style face="normal" font="default" size="100%">Launer, Lenore J</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Montgomery, Grant W</style></author><author><style face="normal" font="default" size="100%">Oostra, Ben A</style></author><author><style face="normal" font="default" size="100%">Ridker, Paul M</style></author><author><style face="normal" font="default" size="100%">Sanna, Serena</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Spector, Tim D</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Streeten, Elizabeth A</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Uda, Manuela</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Völzke, Henry</style></author><author><style face="normal" font="default" size="100%">Murray, Anna</style></author><author><style face="normal" font="default" size="100%">Murabito, Joanne M</style></author><author><style face="normal" font="default" size="100%">Visser, Jenny A</style></author><author><style face="normal" font="default" size="100%">Lunetta, Kathryn L</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">LifeLines Cohort Study</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Age Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Helicases</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Primase</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Repair</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Repair Enzymes</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA-Directed DNA Polymerase</style></keyword><keyword><style  face="normal" font="default" size="100%">European Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Exodeoxyribonucleases</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunity</style></keyword><keyword><style  face="normal" font="default" size="100%">Menopause</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Mar</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">44</style></volume><pages><style face="normal" font="default" size="100%">260-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P &lt; 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22267201?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Elks, Cathy E</style></author><author><style face="normal" font="default" size="100%">Perry, John R B</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Chasman, Daniel I</style></author><author><style face="normal" font="default" size="100%">Franceschini, Nora</style></author><author><style face="normal" font="default" size="100%">He, Chunyan</style></author><author><style face="normal" font="default" size="100%">Lunetta, Kathryn L</style></author><author><style face="normal" font="default" size="100%">Visser, Jenny A</style></author><author><style face="normal" font="default" size="100%">Byrne, Enda M</style></author><author><style face="normal" font="default" size="100%">Cousminer, Diana L</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Feenstra, Bjarke</style></author><author><style face="normal" font="default" size="100%">Hottenga, Jouke-Jan</style></author><author><style face="normal" font="default" size="100%">Koller, Daniel L</style></author><author><style face="normal" font="default" size="100%">Kutalik, Zoltán</style></author><author><style face="normal" font="default" size="100%">Lin, Peng</style></author><author><style face="normal" font="default" size="100%">Mangino, Massimo</style></author><author><style face="normal" font="default" size="100%">Marongiu, Mara</style></author><author><style face="normal" font="default" size="100%">McArdle, Patrick F</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">Stolk, Lisette</style></author><author><style face="normal" font="default" size="100%">van Wingerden, Sophie H</style></author><author><style face="normal" font="default" size="100%">Zhao, Jing Hua</style></author><author><style face="normal" font="default" size="100%">Albrecht, Eva</style></author><author><style face="normal" font="default" size="100%">Corre, Tanguy</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Magnusson, Patrik K E</style></author><author><style face="normal" font="default" size="100%">Smith, Erin N</style></author><author><style face="normal" font="default" size="100%">Ulivi, Shelia</style></author><author><style face="normal" font="default" size="100%">Warrington, Nicole M</style></author><author><style face="normal" font="default" size="100%">Zgaga, Lina</style></author><author><style face="normal" font="default" size="100%">Alavere, Helen</style></author><author><style face="normal" font="default" size="100%">Amin, Najaf</style></author><author><style face="normal" font="default" size="100%">Aspelund, Thor</style></author><author><style face="normal" font="default" size="100%">Bandinelli, Stefania</style></author><author><style face="normal" font="default" size="100%">Barroso, Inês</style></author><author><style face="normal" font="default" size="100%">Berenson, Gerald S</style></author><author><style face="normal" font="default" size="100%">Bergmann, Sven</style></author><author><style face="normal" font="default" size="100%">Blackburn, Hannah</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Buring, Julie E</style></author><author><style face="normal" font="default" size="100%">Busonero, Fabio</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Chanock, Stephen J</style></author><author><style face="normal" font="default" size="100%">Chen, Wei</style></author><author><style face="normal" font="default" size="100%">Cornelis, Marilyn C</style></author><author><style face="normal" font="default" size="100%">Couper, David</style></author><author><style face="normal" font="default" size="100%">Coviello, Andrea D</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">de Faire, Ulf</style></author><author><style face="normal" font="default" size="100%">de Geus, Eco J C</style></author><author><style face="normal" font="default" size="100%">Deloukas, Panos</style></author><author><style face="normal" font="default" size="100%">Döring, Angela</style></author><author><style face="normal" font="default" size="100%">Smith, George Davey</style></author><author><style face="normal" font="default" size="100%">Easton, Douglas F</style></author><author><style face="normal" font="default" size="100%">Eiriksdottir, Gudny</style></author><author><style face="normal" font="default" size="100%">Emilsson, Valur</style></author><author><style face="normal" font="default" size="100%">Eriksson, Johan</style></author><author><style face="normal" font="default" size="100%">Ferrucci, Luigi</style></author><author><style face="normal" font="default" size="100%">Folsom, Aaron R</style></author><author><style face="normal" font="default" size="100%">Foroud, Tatiana</style></author><author><style face="normal" font="default" size="100%">Garcia, Melissa</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Geller, Frank</style></author><author><style face="normal" font="default" size="100%">Gieger, Christian</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Hall, Per</style></author><author><style face="normal" font="default" size="100%">Hankinson, Susan E</style></author><author><style face="normal" font="default" size="100%">Ferreli, Liana</style></author><author><style face="normal" font="default" size="100%">Heath, Andrew C</style></author><author><style face="normal" font="default" size="100%">Hernandez, Dena G</style></author><author><style face="normal" font="default" size="100%">Hofman, Albert</style></author><author><style face="normal" font="default" size="100%">Hu, Frank B</style></author><author><style face="normal" font="default" size="100%">Illig, Thomas</style></author><author><style face="normal" font="default" size="100%">Järvelin, Marjo-Riitta</style></author><author><style face="normal" font="default" size="100%">Johnson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Karasik, David</style></author><author><style face="normal" font="default" size="100%">Khaw, Kay-Tee</style></author><author><style face="normal" font="default" size="100%">Kiel, Douglas P</style></author><author><style face="normal" font="default" size="100%">Kilpeläinen, Tuomas O</style></author><author><style face="normal" font="default" size="100%">Kolcic, Ivana</style></author><author><style face="normal" font="default" size="100%">Kraft, Peter</style></author><author><style face="normal" font="default" size="100%">Launer, Lenore J</style></author><author><style face="normal" font="default" size="100%">Laven, Joop S E</style></author><author><style face="normal" font="default" size="100%">Li, Shengxu</style></author><author><style face="normal" font="default" size="100%">Liu, Jianjun</style></author><author><style face="normal" font="default" size="100%">Levy, Daniel</style></author><author><style face="normal" font="default" size="100%">Martin, Nicholas G</style></author><author><style face="normal" font="default" size="100%">McArdle, Wendy L</style></author><author><style face="normal" font="default" size="100%">Melbye, Mads</style></author><author><style face="normal" font="default" size="100%">Mooser, Vincent</style></author><author><style face="normal" font="default" size="100%">Murray, Jeffrey C</style></author><author><style face="normal" font="default" size="100%">Murray, Sarah S</style></author><author><style face="normal" font="default" size="100%">Nalls, Michael A</style></author><author><style face="normal" font="default" size="100%">Navarro, Pau</style></author><author><style face="normal" font="default" size="100%">Nelis, Mari</style></author><author><style face="normal" font="default" size="100%">Ness, Andrew R</style></author><author><style face="normal" font="default" size="100%">Northstone, Kate</style></author><author><style face="normal" font="default" size="100%">Oostra, Ben A</style></author><author><style face="normal" font="default" size="100%">Peacock, Munro</style></author><author><style face="normal" font="default" size="100%">Palmer, Lyle J</style></author><author><style face="normal" font="default" size="100%">Palotie, Aarno</style></author><author><style face="normal" font="default" size="100%">Paré, Guillaume</style></author><author><style face="normal" font="default" size="100%">Parker, Alex N</style></author><author><style face="normal" font="default" size="100%">Pedersen, Nancy L</style></author><author><style face="normal" font="default" size="100%">Peltonen, Leena</style></author><author><style face="normal" font="default" size="100%">Pennell, Craig E</style></author><author><style face="normal" font="default" size="100%">Pharoah, Paul</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Plump, Andrew S</style></author><author><style face="normal" font="default" size="100%">Pouta, Anneli</style></author><author><style face="normal" font="default" size="100%">Porcu, Eleonora</style></author><author><style face="normal" font="default" size="100%">Rafnar, Thorunn</style></author><author><style face="normal" font="default" size="100%">Rice, John P</style></author><author><style face="normal" font="default" size="100%">Ring, Susan M</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Sala, Cinzia</style></author><author><style face="normal" font="default" size="100%">Salomaa, Veikko</style></author><author><style face="normal" font="default" size="100%">Sanna, Serena</style></author><author><style face="normal" font="default" size="100%">Schlessinger, David</style></author><author><style face="normal" font="default" size="100%">Schork, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Scuteri, Angelo</style></author><author><style face="normal" font="default" size="100%">Segrè, Ayellet V</style></author><author><style face="normal" font="default" size="100%">Shuldiner, Alan R</style></author><author><style face="normal" font="default" size="100%">Soranzo, Nicole</style></author><author><style face="normal" font="default" size="100%">Sovio, Ulla</style></author><author><style face="normal" font="default" size="100%">Srinivasan, Sathanur R</style></author><author><style face="normal" font="default" size="100%">Strachan, David P</style></author><author><style face="normal" font="default" size="100%">Tammesoo, Mar-Liis</style></author><author><style face="normal" font="default" size="100%">Tikkanen, Emmi</style></author><author><style face="normal" font="default" size="100%">Toniolo, Daniela</style></author><author><style face="normal" font="default" size="100%">Tsui, Kim</style></author><author><style face="normal" font="default" size="100%">Tryggvadottir, Laufey</style></author><author><style face="normal" font="default" size="100%">Tyrer, Jonathon</style></author><author><style face="normal" font="default" size="100%">Uda, Manuela</style></author><author><style face="normal" font="default" size="100%">van Dam, Rob M</style></author><author><style face="normal" font="default" size="100%">van Meurs, Joyce B J</style></author><author><style face="normal" font="default" size="100%">Vollenweider, Peter</style></author><author><style face="normal" font="default" size="100%">Waeber, Gerard</style></author><author><style face="normal" font="default" size="100%">Wareham, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Waterworth, Dawn M</style></author><author><style face="normal" font="default" size="100%">Weedon, Michael N</style></author><author><style face="normal" font="default" size="100%">Wichmann, H Erich</style></author><author><style face="normal" font="default" size="100%">Willemsen, Gonneke</style></author><author><style face="normal" font="default" size="100%">Wilson, James F</style></author><author><style face="normal" font="default" size="100%">Wright, Alan F</style></author><author><style face="normal" font="default" size="100%">Young, Lauren</style></author><author><style face="normal" font="default" size="100%">Zhai, Guangju</style></author><author><style face="normal" font="default" size="100%">Zhuang, Wei Vivian</style></author><author><style face="normal" font="default" size="100%">Bierut, Laura J</style></author><author><style face="normal" font="default" size="100%">Boomsma, Dorret I</style></author><author><style face="normal" font="default" size="100%">Boyd, Heather A</style></author><author><style face="normal" font="default" size="100%">Crisponi, Laura</style></author><author><style face="normal" font="default" size="100%">Demerath, Ellen W</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Econs, Michael J</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hunter, David J</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Montgomery, Grant W</style></author><author><style face="normal" font="default" size="100%">Ridker, Paul M</style></author><author><style face="normal" font="default" size="100%">Spector, Tim D</style></author><author><style face="normal" font="default" size="100%">Streeten, Elizabeth A</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André G</style></author><author><style face="normal" font="default" size="100%">Widen, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Murabito, Joanne M</style></author><author><style face="normal" font="default" size="100%">Ong, Ken K</style></author><author><style face="normal" font="default" size="100%">Murray, Anna</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">GIANT Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Aging</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Height</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Size</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Copy Number Variations</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inheritance Patterns</style></keyword><keyword><style  face="normal" font="default" size="100%">Menarche</style></keyword><keyword><style  face="normal" font="default" size="100%">Obesity</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Reproducibility of Results</style></keyword><keyword><style  face="normal" font="default" size="100%">Time Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">42</style></volume><pages><style face="normal" font="default" size="100%">1077-85</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P &lt; 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P &lt; 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21102462?dopt=Abstract</style></custom1></record></records></xml>