<?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%">Marouli, Eirini</style></author><author><style face="normal" font="default" size="100%">Graff, Mariaelisa</style></author><author><style face="normal" font="default" size="100%">Medina-Gomez, Carolina</style></author><author><style face="normal" font="default" size="100%">Lo, Ken Sin</style></author><author><style face="normal" font="default" size="100%">Wood, Andrew R</style></author><author><style face="normal" font="default" size="100%">Kjaer, Troels R</style></author><author><style face="normal" font="default" size="100%">Fine, Rebecca S</style></author><author><style face="normal" font="default" size="100%">Lu, Yingchang</style></author><author><style face="normal" font="default" size="100%">Schurmann, Claudia</style></author><author><style face="normal" font="default" size="100%">Highland, Heather M</style></author><author><style face="normal" font="default" size="100%">Rüeger, Sina</style></author><author><style face="normal" font="default" size="100%">Thorleifsson, Gudmar</style></author><author><style face="normal" font="default" size="100%">Justice, Anne E</style></author><author><style face="normal" font="default" size="100%">Lamparter, David</style></author><author><style face="normal" font="default" size="100%">Stirrups, Kathleen E</style></author><author><style face="normal" font="default" size="100%">Turcot, Valérie</style></author><author><style face="normal" font="default" size="100%">Young, Kristin L</style></author><author><style face="normal" font="default" size="100%">Winkler, Thomas W</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Karaderi, Tugce</style></author><author><style face="normal" font="default" size="100%">Locke, Adam E</style></author><author><style face="normal" font="default" size="100%">Masca, Nicholas G D</style></author><author><style face="normal" font="default" size="100%">Ng, Maggie C Y</style></author><author><style face="normal" font="default" size="100%">Mudgal, Poorva</style></author><author><style face="normal" font="default" size="100%">Rivas, Manuel A</style></author><author><style face="normal" font="default" size="100%">Vedantam, Sailaja</style></author><author><style face="normal" font="default" size="100%">Mahajan, Anubha</style></author><author><style face="normal" font="default" size="100%">Guo, Xiuqing</style></author><author><style face="normal" font="default" size="100%">Abecasis, Goncalo</style></author><author><style face="normal" font="default" size="100%">Aben, Katja K</style></author><author><style face="normal" font="default" size="100%">Adair, Linda S</style></author><author><style face="normal" font="default" size="100%">Alam, Dewan S</style></author><author><style face="normal" font="default" size="100%">Albrecht, Eva</style></author><author><style face="normal" font="default" size="100%">Allin, Kristine H</style></author><author><style face="normal" font="default" size="100%">Allison, Matthew</style></author><author><style face="normal" font="default" size="100%">Amouyel, Philippe</style></author><author><style face="normal" font="default" size="100%">Appel, Emil V</style></author><author><style face="normal" font="default" size="100%">Arveiler, 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Eric</style></author><author><style face="normal" font="default" size="100%">Böger, Carsten A</style></author><author><style face="normal" font="default" size="100%">Bonnycastle, Lori L</style></author><author><style face="normal" font="default" size="100%">Bork-Jensen, Jette</style></author><author><style face="normal" font="default" size="100%">Bots, Michiel L</style></author><author><style face="normal" font="default" size="100%">Bottinger, Erwin P</style></author><author><style face="normal" font="default" size="100%">Bowden, Donald W</style></author><author><style face="normal" font="default" size="100%">Brandslund, Ivan</style></author><author><style face="normal" font="default" size="100%">Breen, Gerome</style></author><author><style face="normal" font="default" size="100%">Brilliant, Murray H</style></author><author><style face="normal" font="default" size="100%">Broer, Linda</style></author><author><style face="normal" font="default" size="100%">Burt, Amber 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M</style></author><author><style face="normal" font="default" size="100%">Ferrières, Jean</style></author><author><style face="normal" font="default" size="100%">Florez, Jose C</style></author><author><style face="normal" font="default" size="100%">Ford, Ian</style></author><author><style face="normal" font="default" size="100%">Fornage, Myriam</style></author><author><style face="normal" font="default" size="100%">Franks, Paul W</style></author><author><style face="normal" font="default" size="100%">Frikke-Schmidt, Ruth</style></author><author><style face="normal" font="default" size="100%">Galesloot, Tessel E</style></author><author><style face="normal" font="default" size="100%">Gan, Wei</style></author><author><style face="normal" font="default" size="100%">Gandin, Ilaria</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Giedraitis, Vilmantas</style></author><author><style face="normal" font="default" size="100%">Giri, Ayush</style></author><author><style face="normal" font="default" size="100%">Girotto, Giorgia</style></author><author><style face="normal" font="default" size="100%">Gordon, Scott D</style></author><author><style face="normal" font="default" size="100%">Gordon-Larsen, Penny</style></author><author><style face="normal" font="default" size="100%">Gorski, Mathias</style></author><author><style face="normal" font="default" size="100%">Grarup, Niels</style></author><author><style face="normal" font="default" size="100%">Grove, Megan L</style></author><author><style face="normal" font="default" size="100%">Gudnason, Vilmundur</style></author><author><style face="normal" font="default" size="100%">Gustafsson, Stefan</style></author><author><style face="normal" font="default" size="100%">Hansen, Torben</style></author><author><style face="normal" font="default" size="100%">Harris, Kathleen Mullan</style></author><author><style face="normal" font="default" size="100%">Harris, Tamara B</style></author><author><style face="normal" font="default" size="100%">Hattersley, Andrew T</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">He, Liang</style></author><author><style face="normal" font="default" size="100%">Heid, Iris M</style></author><author><style face="normal" font="default" size="100%">Heikkilä, Kauko</style></author><author><style face="normal" font="default" size="100%">Helgeland, Øyvind</style></author><author><style face="normal" font="default" size="100%">Hernesniemi, Jussi</style></author><author><style face="normal" font="default" size="100%">Hewitt, Alex W</style></author><author><style face="normal" font="default" size="100%">Hocking, Lynne J</style></author><author><style face="normal" font="default" size="100%">Hollensted, Mette</style></author><author><style face="normal" font="default" size="100%">Holmen, Oddgeir L</style></author><author><style face="normal" font="default" size="100%">Hovingh, G Kees</style></author><author><style face="normal" font="default" size="100%">Howson, Joanna M M</style></author><author><style face="normal" font="default" size="100%">Hoyng, Carel B</style></author><author><style face="normal" font="default" size="100%">Huang, Paul L</style></author><author><style face="normal" font="default" size="100%">Hveem, Kristian</style></author><author><style face="normal" font="default" size="100%">Ikram, M Arfan</style></author><author><style face="normal" font="default" size="100%">Ingelsson, Erik</style></author><author><style face="normal" font="default" size="100%">Jackson, Anne U</style></author><author><style face="normal" font="default" size="100%">Jansson, Jan-Håkan</style></author><author><style face="normal" font="default" size="100%">Jarvik, Gail P</style></author><author><style face="normal" font="default" size="100%">Jensen, Gorm B</style></author><author><style face="normal" font="default" size="100%">Jhun, Min A</style></author><author><style face="normal" font="default" size="100%">Jia, Yucheng</style></author><author><style face="normal" font="default" size="100%">Jiang, Xuejuan</style></author><author><style face="normal" font="default" size="100%">Johansson, Stefan</style></author><author><style face="normal" font="default" size="100%">Jørgensen, Marit E</style></author><author><style face="normal" font="default" size="100%">Jørgensen, Torben</style></author><author><style face="normal" font="default" size="100%">Jousilahti, Pekka</style></author><author><style face="normal" font="default" size="100%">Jukema, J Wouter</style></author><author><style face="normal" font="default" size="100%">Kahali, Bratati</style></author><author><style face="normal" font="default" size="100%">Kahn, René S</style></author><author><style face="normal" font="default" size="100%">Kähönen, Mika</style></author><author><style face="normal" font="default" size="100%">Kamstrup, Pia R</style></author><author><style face="normal" font="default" size="100%">Kanoni, Stavroula</style></author><author><style face="normal" font="default" size="100%">Kaprio, Jaakko</style></author><author><style face="normal" font="default" size="100%">Karaleftheri, Maria</style></author><author><style face="normal" font="default" size="100%">Kardia, Sharon L R</style></author><author><style face="normal" font="default" size="100%">Karpe, Fredrik</style></author><author><style face="normal" font="default" size="100%">Kee, Frank</style></author><author><style face="normal" font="default" size="100%">Keeman, Renske</style></author><author><style face="normal" font="default" size="100%">Kiemeney, Lambertus A</style></author><author><style face="normal" font="default" size="100%">Kitajima, Hidetoshi</style></author><author><style face="normal" font="default" size="100%">Kluivers, Kirsten B</style></author><author><style face="normal" font="default" size="100%">Kocher, Thomas</style></author><author><style face="normal" font="default" size="100%">Komulainen, Pirjo</style></author><author><style face="normal" font="default" size="100%">Kontto, Jukka</style></author><author><style face="normal" font="default" size="100%">Kooner, Jaspal S</style></author><author><style face="normal" font="default" size="100%">Kooperberg, Charles</style></author><author><style face="normal" font="default" size="100%">Kovacs, Peter</style></author><author><style face="normal" font="default" size="100%">Kriebel, Jennifer</style></author><author><style face="normal" font="default" size="100%">Kuivaniemi, Helena</style></author><author><style face="normal" font="default" size="100%">Küry, Sébastien</style></author><author><style face="normal" font="default" size="100%">Kuusisto, Johanna</style></author><author><style face="normal" font="default" size="100%">La Bianca, Martina</style></author><author><style face="normal" font="default" size="100%">Laakso, Markku</style></author><author><style face="normal" font="default" size="100%">Lakka, Timo A</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%">Langefeld, Carl D</style></author><author><style face="normal" font="default" size="100%">Langenberg, Claudia</style></author><author><style face="normal" font="default" size="100%">Larson, Eric B</style></author><author><style face="normal" font="default" size="100%">Lee, I-Te</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho</style></author><author><style face="normal" font="default" size="100%">Lewis, Cora E</style></author><author><style face="normal" font="default" size="100%">Li, Huaixing</style></author><author><style face="normal" font="default" size="100%">Li, 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size="100%">Walker, Mark</style></author><author><style face="normal" font="default" size="100%">Wang, Feijie</style></author><author><style face="normal" font="default" size="100%">Wang, Carol A</style></author><author><style face="normal" font="default" size="100%">Wang, Shuai</style></author><author><style face="normal" font="default" size="100%">Wang, Yiqin</style></author><author><style face="normal" font="default" size="100%">Wareham, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Warren, Helen R</style></author><author><style face="normal" font="default" size="100%">Wessel, Jennifer</style></author><author><style face="normal" font="default" size="100%">Willems, Sara M</style></author><author><style face="normal" font="default" size="100%">Wilson, James G</style></author><author><style face="normal" font="default" size="100%">Witte, Daniel R</style></author><author><style face="normal" font="default" size="100%">Woods, Michael 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font="default" size="100%">Zhao, Wei</style></author><author><style face="normal" font="default" size="100%">Zheng, He</style></author><author><style face="normal" font="default" size="100%">Zhou, Wei</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Boehnke, Michael</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author><author><style face="normal" font="default" size="100%">McCarthy, Mark I</style></author><author><style face="normal" font="default" size="100%">Willer, Cristen J</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author><author><style face="normal" font="default" size="100%">Borecki, Ingrid B</style></author><author><style face="normal" font="default" size="100%">Liu, Dajiang J</style></author><author><style face="normal" font="default" size="100%">North, Kari E</style></author><author><style face="normal" font="default" size="100%">Heard-Costa, Nancy L</style></author><author><style face="normal" font="default" size="100%">Pers, Tune H</style></author><author><style face="normal" font="default" size="100%">Lindgren, Cecilia M</style></author><author><style face="normal" font="default" size="100%">Oxvig, Claus</style></author><author><style face="normal" font="default" size="100%">Kutalik, Zoltán</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Frayling, Timothy M</style></author><author><style face="normal" font="default" size="100%">Hirschhorn, Joel N</style></author><author><style face="normal" font="default" size="100%">Deloukas, Panos</style></author><author><style face="normal" font="default" size="100%">Lettre, Guillaume</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%">CHD Exome+ Consortium</style></author><author><style face="normal" font="default" size="100%">ExomeBP Consortium</style></author><author><style face="normal" font="default" size="100%">T2D-Genes Consortium</style></author><author><style face="normal" font="default" size="100%">GoT2D Genes Consortium</style></author><author><style face="normal" font="default" size="100%">Global Lipids Genetics Consortium</style></author><author><style face="normal" font="default" size="100%">ReproGen Consortium</style></author><author><style face="normal" font="default" size="100%">MAGIC Investigators</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Rare and low-frequency coding variants alter human adult height.</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%">ADAMTS Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Height</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Adhesion Molecules</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Glycoproteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Glycosaminoglycans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hedgehog Proteins</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%">Interferon Regulatory Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Interleukin-11 Receptor alpha Subunit</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword><keyword><style  face="normal" font="default" size="100%">NADPH Oxidase 4</style></keyword><keyword><style  face="normal" font="default" size="100%">NADPH Oxidases</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Pregnancy-Associated Plasma Protein-A</style></keyword><keyword><style  face="normal" font="default" size="100%">Procollagen N-Endopeptidase</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteoglycans</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteolysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Androgen</style></keyword><keyword><style  face="normal" font="default" size="100%">Somatomedins</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 02 09</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">542</style></volume><pages><style face="normal" font="default" size="100%">186-190</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7640</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract</style></custom1></record></records></xml>