<?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%">Shah, Rupal L</style></author><author><style face="normal" font="default" size="100%">Li, Qing</style></author><author><style face="normal" font="default" size="100%">Zhao, Wanting</style></author><author><style face="normal" font="default" size="100%">Tedja, Milly S</style></author><author><style face="normal" font="default" size="100%">Tideman, J Willem L</style></author><author><style face="normal" font="default" size="100%">Khawaja, Anthony P</style></author><author><style face="normal" font="default" size="100%">Fan, Qiao</style></author><author><style face="normal" font="default" size="100%">Yazar, Seyhan</style></author><author><style face="normal" font="default" size="100%">Williams, Katie M</style></author><author><style face="normal" font="default" size="100%">Verhoeven, Virginie J M</style></author><author><style face="normal" font="default" size="100%">Xie, Jing</style></author><author><style face="normal" font="default" size="100%">Wang, Ya Xing</style></author><author><style face="normal" font="default" size="100%">Hess, Moritz</style></author><author><style face="normal" font="default" size="100%">Nickels, Stefan</style></author><author><style face="normal" font="default" size="100%">Lackner, Karl J</style></author><author><style face="normal" font="default" size="100%">Pärssinen, Olavi</style></author><author><style face="normal" font="default" size="100%">Wedenoja, Juho</style></author><author><style face="normal" font="default" size="100%">Biino, Ginevra</style></author><author><style face="normal" font="default" size="100%">Concas, Maria Pina</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Jaddoe, Vincent W V</style></author><author><style face="normal" font="default" size="100%">Hysi, Pirro G</style></author><author><style face="normal" font="default" size="100%">Sim, Xueling</style></author><author><style face="normal" font="default" size="100%">Tan, Nicholas</style></author><author><style face="normal" font="default" size="100%">Tham, Yih-Chung</style></author><author><style face="normal" font="default" size="100%">Sensaki, Sonoko</style></author><author><style face="normal" font="default" size="100%">Hofman, Albert</style></author><author><style face="normal" font="default" size="100%">Vingerling, Johannes R</style></author><author><style face="normal" font="default" size="100%">Jonas, Jost B</style></author><author><style face="normal" font="default" size="100%">Mitchell, Paul</style></author><author><style face="normal" font="default" size="100%">Hammond, Christopher J</style></author><author><style face="normal" font="default" size="100%">Höhn, René</style></author><author><style face="normal" font="default" size="100%">Baird, Paul N</style></author><author><style face="normal" font="default" size="100%">Wong, Tien-Yin</style></author><author><style face="normal" font="default" size="100%">Cheng, Chinfsg-Yu</style></author><author><style face="normal" font="default" size="100%">Teo, Yik Ying</style></author><author><style face="normal" font="default" size="100%">Mackey, David A</style></author><author><style face="normal" font="default" size="100%">Williams, Cathy</style></author><author><style face="normal" font="default" size="100%">Saw, Seang-Mei</style></author><author><style face="normal" font="default" size="100%">Klaver, Caroline C W</style></author><author><style face="normal" font="default" size="100%">Guggenheim, Jeremy A</style></author><author><style face="normal" font="default" size="100%">Bailey-Wilson, Joan E</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">CREAM Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">A genome-wide association study of corneal astigmatism: The CREAM Consortium.</style></title><secondary-title><style face="normal" font="default" size="100%">Mol Vis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol. Vis.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Acid Phosphatase</style></keyword><keyword><style  face="normal" font="default" size="100%">Asian Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Astigmatism</style></keyword><keyword><style  face="normal" font="default" size="100%">Claudins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Cornea</style></keyword><keyword><style  face="normal" font="default" size="100%">Corneal Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">European Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</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%">Intracellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Odds Ratio</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Platelet-Derived Growth Factor alpha</style></keyword><keyword><style  face="normal" font="default" size="100%">Software</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</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">24</style></volume><pages><style face="normal" font="default" size="100%">127-142</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;Purpose: &lt;/b&gt;To identify genes and genetic markers associated with corneal astigmatism.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods: &lt;/b&gt;A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having &gt;0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results: &lt;/b&gt;The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha () gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (), acid phosphatase 2, lysosomal (), and TNF alpha-induced protein 8 like 3 ().&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions: &lt;/b&gt;In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the  gene, gene-based analysis identified three novel candidate genes, , , and , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/29422769?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%">McQuillan, Ruth</style></author><author><style face="normal" font="default" size="100%">Eklund, Niina</style></author><author><style face="normal" font="default" size="100%">Pirastu, Nicola</style></author><author><style face="normal" font="default" size="100%">Kuningas, Maris</style></author><author><style face="normal" font="default" size="100%">McEvoy, Brian P</style></author><author><style face="normal" font="default" size="100%">Esko, Tõnu</style></author><author><style face="normal" font="default" size="100%">Corre, Tanguy</style></author><author><style face="normal" font="default" size="100%">Davies, Gail</style></author><author><style face="normal" font="default" size="100%">Kaakinen, Marika</style></author><author><style face="normal" font="default" size="100%">Lyytikäinen, Leo-Pekka</style></author><author><style face="normal" font="default" size="100%">Kristiansson, Kati</style></author><author><style face="normal" font="default" size="100%">Havulinna, Aki S</style></author><author><style face="normal" font="default" size="100%">Gögele, Martin</style></author><author><style face="normal" font="default" size="100%">Vitart, Veronique</style></author><author><style face="normal" font="default" size="100%">Tenesa, Albert</style></author><author><style face="normal" font="default" size="100%">Aulchenko, Yurii</style></author><author><style face="normal" font="default" size="100%">Hayward, Caroline</style></author><author><style face="normal" font="default" size="100%">Johansson, Åsa</style></author><author><style face="normal" font="default" size="100%">Boban, Mladen</style></author><author><style face="normal" font="default" size="100%">Ulivi, Sheila</style></author><author><style face="normal" font="default" size="100%">Robino, Antonietta</style></author><author><style face="normal" font="default" size="100%">Boraska, Vesna</style></author><author><style face="normal" font="default" size="100%">Igl, Wilmar</style></author><author><style face="normal" font="default" size="100%">Wild, Sarah H</style></author><author><style face="normal" font="default" size="100%">Zgaga, Lina</style></author><author><style face="normal" font="default" size="100%">Amin, Najaf</style></author><author><style face="normal" font="default" size="100%">Theodoratou, Evropi</style></author><author><style face="normal" font="default" size="100%">Polasek, Ozren</style></author><author><style face="normal" font="default" size="100%">Girotto, Giorgia</style></author><author><style face="normal" font="default" size="100%">Lopez, Lorna M</style></author><author><style face="normal" font="default" size="100%">Sala, Cinzia</style></author><author><style face="normal" font="default" size="100%">Lahti, Jari</style></author><author><style face="normal" font="default" size="100%">Laatikainen, Tiina</style></author><author><style face="normal" font="default" size="100%">Prokopenko, Inga</style></author><author><style face="normal" font="default" size="100%">Kals, Mart</style></author><author><style face="normal" font="default" size="100%">Viikari, Jorma</style></author><author><style face="normal" font="default" size="100%">Yang, Jian</style></author><author><style face="normal" font="default" size="100%">Pouta, Anneli</style></author><author><style face="normal" font="default" size="100%">Estrada, Karol</style></author><author><style face="normal" font="default" size="100%">Hofman, Albert</style></author><author><style face="normal" font="default" size="100%">Freimer, Nelson</style></author><author><style face="normal" font="default" size="100%">Martin, Nicholas G</style></author><author><style face="normal" font="default" size="100%">Kähönen, Mika</style></author><author><style face="normal" font="default" size="100%">Milani, Lili</style></author><author><style face="normal" font="default" size="100%">Heliövaara, Markku</style></author><author><style face="normal" font="default" size="100%">Vartiainen, Erkki</style></author><author><style face="normal" font="default" size="100%">Räikkönen, Katri</style></author><author><style face="normal" font="default" size="100%">Masciullo, Corrado</style></author><author><style face="normal" font="default" size="100%">Starr, John M</style></author><author><style face="normal" font="default" size="100%">Hicks, Andrew A</style></author><author><style face="normal" font="default" size="100%">Esposito, Laura</style></author><author><style face="normal" font="default" size="100%">Kolcic, Ivana</style></author><author><style face="normal" font="default" size="100%">Farrington, Susan M</style></author><author><style face="normal" font="default" size="100%">Oostra, Ben</style></author><author><style face="normal" font="default" size="100%">Zemunik, Tatijana</style></author><author><style face="normal" font="default" size="100%">Campbell, Harry</style></author><author><style face="normal" font="default" size="100%">Kirin, Mirna</style></author><author><style face="normal" font="default" size="100%">Pehlic, Marina</style></author><author><style face="normal" font="default" size="100%">Faletra, Flavio</style></author><author><style face="normal" font="default" size="100%">Porteous, David</style></author><author><style face="normal" font="default" size="100%">Pistis, Giorgio</style></author><author><style face="normal" font="default" size="100%">Widen, Elisabeth</style></author><author><style face="normal" font="default" size="100%">Salomaa, Veikko</style></author><author><style face="normal" font="default" size="100%">Koskinen, Seppo</style></author><author><style face="normal" font="default" size="100%">Fischer, Krista</style></author><author><style face="normal" font="default" size="100%">Lehtimäki, Terho</style></author><author><style face="normal" font="default" size="100%">Heath, Andrew</style></author><author><style face="normal" font="default" size="100%">McCarthy, Mark I</style></author><author><style face="normal" font="default" size="100%">Rivadeneira, Fernando</style></author><author><style face="normal" font="default" size="100%">Montgomery, Grant W</style></author><author><style face="normal" font="default" size="100%">Tiemeier, Henning</style></author><author><style face="normal" font="default" size="100%">Hartikainen, Anna-Liisa</style></author><author><style face="normal" font="default" size="100%">Madden, Pamela A F</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">Hastie, Nicholas D</style></author><author><style face="normal" font="default" size="100%">Gyllensten, Ulf</style></author><author><style face="normal" font="default" size="100%">Wright, Alan F</style></author><author><style face="normal" font="default" size="100%">van Duijn, Cornelia M</style></author><author><style face="normal" font="default" size="100%">Dunlop, Malcolm</style></author><author><style face="normal" font="default" size="100%">Rudan, Igor</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Pramstaller, Peter P</style></author><author><style face="normal" font="default" size="100%">Deary, Ian J</style></author><author><style face="normal" font="default" size="100%">Toniolo, Daniela</style></author><author><style face="normal" font="default" size="100%">Eriksson, Johan G</style></author><author><style face="normal" font="default" size="100%">Jula, Antti</style></author><author><style face="normal" font="default" size="100%">Raitakari, Olli T</style></author><author><style face="normal" font="default" size="100%">Metspalu, Andres</style></author><author><style face="normal" font="default" size="100%">Perola, Markus</style></author><author><style face="normal" font="default" size="100%">Järvelin, Marjo-Riitta</style></author><author><style face="normal" font="default" size="100%">Uitterlinden, André</style></author><author><style face="normal" font="default" size="100%">Visscher, Peter M</style></author><author><style face="normal" font="default" size="100%">Wilson, James F</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">ROHgen Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Evidence of inbreeding depression on human height.</style></title><secondary-title><style face="normal" font="default" size="100%">PLoS Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">PLoS 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%">Body Height</style></keyword><keyword><style  face="normal" font="default" size="100%">Consanguinity</style></keyword><keyword><style  face="normal" font="default" size="100%">Databases, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Family</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Recessive</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Heterogeneity</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Homozygote</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%">Middle Aged</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, Heritable</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</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">e1002655</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Stature is a classical and highly heritable complex trait, with 80%-90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ(2) = 83.89, df = 1; p = 5.2 × 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22829771?dopt=Abstract</style></custom1></record></records></xml>