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Defining the role of common variation in the genomic and biological architecture of adult human height.

Wood, Andrew R; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H; Gustafsson, Stefan; Chu, Audrey Y; Estrada, Karol; Luan, Jian'an and Kutalik, Zoltán, et al. (2014) In Nature Genetics 46(11). p.1173-1186
Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We... (More)
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. (Less)
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46
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11
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  • pmid:25282103
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  • scopus:84908890496
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1546-1718
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10.1038/ng.3097
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@article{3eef2a04-5cff-4954-bb97-af39afe17a15,
  abstract     = {Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.},
  author       = {Wood, Andrew R and Esko, Tonu and Yang, Jian and Vedantam, Sailaja and Pers, Tune H and Gustafsson, Stefan and Chu, Audrey Y and Estrada, Karol and Luan, Jian'an and Kutalik, Zoltán and Amin, Najaf and Buchkovich, Martin L and Croteau-Chonka, Damien C and Day, Felix R and Duan, Yanan and Fall, Tove and Fehrmann, Rudolf and Ferreira, Teresa and Jackson, Anne U and Karjalainen, Juha and Lo, Ken Sin and Locke, Adam E and Mägi, Reedik and Mihailov, Evelin and Porcu, Eleonora and Randall, Joshua C and Scherag, André and Vinkhuyzen, Anna A E and Westra, Harm-Jan and Winkler, Thomas W and Workalemahu, Tsegaselassie and Zhao, Jing Hua and Absher, Devin and Albrecht, Eva and Anderson, Denise and Baron, Jeffrey and Beekman, Marian and Demirkan, Ayse and Ehret, Georg B and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Fraser, Ross M and Goel, Anuj and Gong, Jian and Justice, Anne E and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Lui, Julian C and Mangino, Massimo and Mateo Leach, Irene and Medina-Gomez, Carolina and Nalls, Michael A and Nyholt, Dale R and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Prokopenko, Inga and Ried, Janina S and Ripke, Stephan and Shungin, Dmitry and Stancáková, Alena and Strawbridge, Rona J and Sung, Yun Ju and Tanaka, Toshiko and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Van Vliet-Ostaptchouk, Jana V and Wang, Zhaoming and Yengo, Loïc and Zhang, Weihua and Afzal, Uzma and Arnlöv, Johan and Arscott, Gillian M and Bandinelli, Stefania and Barrett, Amy and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blüher, Matthias and Bolton, Jennifer L and Böttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Buckley, Brendan M and Buyske, Steven and Caspersen, Ida H and Chines, Peter S and Clarke, Robert and Claudi-Boehm, Simone and Cooper, Matthew and Daw, E Warwick and De 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and Steinthorsdottir, Valgerdur and Stolk, Ronald P and Tardif, Jean-Claude and Tönjes, Anke and Tremblay, Angelo and Tremoli, Elena and Virtamo, Jarmo and Vohl, Marie-Claude and Amouyel, Philippe and Asselbergs, Folkert W and Assimes, Themistocles L and Bochud, Murielle and Boehm, Bernhard O and Boerwinkle, Eric and Bottinger, Erwin P and Bouchard, Claude and Cauchi, Stéphane and Chambers, John C and Chanock, Stephen J and Cooper, Richard S and de Bakker, Paul I W and Dedoussis, George and Ferrucci, Luigi and Franks, Paul and Froguel, Philippe and Groop, Leif and Haiman, Christopher A and Hamsten, Anders and Hayes, M Geoffrey and Hui, Jennie and Hunter, David J and Hveem, Kristian and Jukema, J Wouter and Kaplan, Robert C and Kivimaki, Mika and Kuh, Diana and Laakso, Markku and Liu, Yongmei and Martin, Nicholas G and März, Winfried and Melbye, Mads and Moebus, Susanne and Munroe, Patricia B and Njølstad, Inger and Oostra, Ben A and Palmer, Colin N A and Pedersen, Nancy L and Perola, 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M and Franke, Lude and Willer, Cristen J and Price, Alkes L and Lettre, Guillaume and Loos, Ruth J F and Weedon, Michael N and Ingelsson, Erik and O'Connell, Jeffrey R and Abecasis, Goncalo R and Chasman, Daniel I and Goddard, Michael E and Visscher, Peter M and Hirschhorn, Joel N and Frayling, Timothy M},
  issn         = {1546-1718},
  language     = {eng},
  number       = {11},
  pages        = {1173--1186},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Defining the role of common variation in the genomic and biological architecture of adult human height.},
  url          = {http://dx.doi.org/10.1038/ng.3097},
  volume       = {46},
  year         = {2014},
}