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Hundreds of variants clustered in genomic loci and biological pathways affect human height
Authors :
Allen, H.L. Estrada Gil, K. (Karol) Lettre, G. (Guillaume) Berndt, S.I. (Sonja) Rivadeneira Ramirez, F. (Fernando) Willer, C.J. (Cristen) Jackson, A.U. (Anne) Vedantam, S. (Sailaja) Raychaudhuri, S. (Soumya) Ferreira, T. (Teresa) Wood, A.R. (Andrew) Weyant, R.J. (Robert) Segrè, A.V. (Ayellet) Speliotes, E.K. (Elizabeth) Wheeler, E. (Eleanor) Soranzo, N. (Nicole) Park, J.H. Yang, J. (Joanna) Gudbjartsson, D.F. (Daniel) Heard-Costa, N.L. (Nancy) Randall, J.C. (Joshua) Qi, L. (Lu) Smith, A.V. (Albert Vernon) Mägi, R. (Reedik) Pastinen, T. (Tomi) Liang, L. (Liming) Heid, I.M. (Iris) Luan, J. Thorleifsson, G. (Gudmar) Winkler, T.W. (Thomas) Goddard, M.E. (Michael) Lo, K.S. Palmer, C. (Cameron) Workalemahu, T. (Tsegaselassie) Aulchenko, Y.S. (Yurii) Johansson, A. (Åsa) Zillikens, M.C. (Carola) Feitosa, M.F. (Mary Furlan) Esko, T. (Tõnu) Johnson, T. (Toby) Ketkar, S. (Shamika) Kraft, P. (Peter) Mangino, M. (Massimo) Prokopenko, I. (Inga) Absher, D. (Devin) Albrecht, E. (Eva) Ernst, F.D.J. (Florian) Glazer, N.L. (Nicole) Hayward, C. (Caroline) Hottenga, J.J. (Jouke Jan) Jacobs, K.B. (Kevin) Knowles, J.W. (Joshua) Kutalik, Z. (Zoltán) Monda, K.L. (Keri) Polasek, O. (Ozren) Preuss, M. (Michael) Rayner, N.W. (Nigel William) Robertson, N.R. (Neil) Steinthorsdottir, V. (Valgerdur) Tyrer, J.P. (Jonathan) Voight, B.F. (Benjamin) Wiklund, F. (Fredrik) Xu, J. (Jianfeng) Zhao, J.H. (Jing Hua) Nyholt, D.R. (Dale) Pellikka, N. (Niina) Perola, M. (Markus) Perry, J.R.B. (John) Surakka, I. (Ida) Tammesoo, M.L. Altmaier, E.L. (Elizabeth) Amin, N. (Najaf) Aspelund, T. (Thor) Bhangale, T. (Tushar) Boucher, G. (Gabrielle) Chasman, D.I. (Daniel) Chen, C. (Constance) Coin, L. (Lachlan) Cooper, M.N. (Matthew) Dixon, A.L. (Anna) Gibson, Q. (Quince) Grundberg, E. (Elin) Hao, K. (Ke) Junttila, M.J. (Juhani) Kaplan, R.C. (Robert) Kettunen, J. (Johannes) König, I.R. (Inke) Kwan, T. (Tony) Lawrence, R.W. (Robert) Levinson, D.F. (Douglas) Lorentzon, M. (Mattias) McKnight, B. (Barbara) Morris, A.D. (Andrew) Müller, M. (Martina) Ngwa, J.S. Purcell, S. (Shaun) Rafelt, S. (Suzanne) Salem, R.M. (Rany) Salvi, E. (Erika) Sanna, S. (Serena) Shi, J. (Jianxin) Sovio, U. (Ulla) Thompson, J.R. (John) Turchin, M.C. (Michael) Vandenput, L. (Liesbeth) Verlaan, D.J. (Dominique) Vitart, V. (Veronique) White, C.C. (Charles) Ziegler, A. (Andreas) Almgren, P. (Peter) Balmforth, A.J. (Anthony) Campbell, H. (Harry) Citterio, L. (Lorena) Grandi, A. (Alessandro) de Dominiczak, A. (Anna) Duan, J. (Jubao) Elliott, P. (Paul) Elosua, R. (Roberto) Eriksson, J.G. (Johan) Freimer, N.B. (Nelson) Geus, E.J.C. (Eco) de Glorioso, N. (Nicola) Haiqing, S. (Shen) Hartikainen, A.L. Havulinna, A.S. (Aki) Hicks, A.A. (Andrew) Hui, J. (Jennie) Igl, W. (Wilmar) Illig, T. (Thomas) Jula, A. (Antti) Kajantie, E. (Eero) Kilpeläinen, T.O. (Tuomas) Koiranen, M. (Markku) Kolcic, I. (Ivana) Koskinen, S. (Seppo) Kovacs, P. (Peter) Laitinen, J. (Jaana) Liu, J. (Jianjun) Lokki, M.L. Marusic, A. (Ana) Maschio, A. Meitinger, T. (Thomas) Mulas, A. (Antonella) Paré, G. (Guillaume) Parker, A.N. (Alex) Peden, J. (John) Petersmann, A. (Astrid) Pichler, I. (Irene) Pietilainen, K.H. (Kirsi Hannele) Pouta, A. (Anneli) Ridderstråle, M. (Martin) Rotter, J.I. (Jerome) Sambrook, J.G. (Jennifer) Sanders, A.R. (Alan) Schmidt, C.O. (Carsten Oliver) Sinisalo, J. (Juha) Smit, J.H. (Jan) Stringham, H.M. (Heather) Walters, G.B. (Bragi) Widen, E. (Elisabeth) Wild, S.H. (Sarah) Willemsen, G.A.H.M. (Gonneke) Zagato, L. (Laura) Zgaga, L. (Lina) Zitting, P. (Paavo) Alavere, H. (Helene) Farrall, M. (Martin) McArdle, W.L. (Wendy) Nelis, M. (Mari) Peters, M.J. (Marjolein) Ripatti, S. (Samuli) Meurs, J.B.J. (Joyce) van Aben, K.K.H. (Katja) Beckmann, J.S. (Jacques) Beilby, J.P. (John) Bergman, R.N. (Richard) Bergmann, S.M. (Sven) Collins, F.S. (Francis) Cusi, D. (Daniele) Heijer, M. (Martin) den Eiriksdottir, G. (Gudny) Gejman, P.V. (Pablo) Hall, A.S. (Alistair) Hamsten, A. (Anders) Huikuri, H.V. (Heikki) Iribarren, C. (Carlos) Kähönen, M. (Mika) Kaprio, J. (Jaakko) Kathiresan, S. (Sekar) Kiemeney, L.A.L.M. (Bart) Kocher, T. (Thomas) Launer, L.J. (Lenore) Lehtimäki, T. (Terho) Melander, O. (Olle) Mosley, T.H. (Thomas) Musk, A.W. (Arthur) Nieminen, M.S. (Markku) O'Donnell, C.J. (Christopher) Ohlsson, C. (Claes) Oostra, B.A. (Ben) Raitakari, O. (Olli) Ridker, P.M. (Paul) Rioux, J.D. (John) Rissanen, A. (Aila) Rivolta, C. (Carlo) Schunkert, H. (Heribert) Shuldiner, A.R. (Alan) Siscovick, D.S. (David) Stumvoll, M. (Michael) Tönjes, A. (Anke) Tuomilehto, J. (Jaakko) Ommen, G.J. (Gert) van Viikari, J. (Jorma) Heath, A.C. (Andrew) Martin, N.G. (Nicholas) Montgomery, G.W. (Grant) Province, M.A. (Mike) Kayser, M.H. (Manfred) Arnold, A.M. (Alice) Atwood, L.D. (Larry) Boerwinkle, E.A. (Eric) Chanock, S.J. (Stephen) Deloukas, P. (Panagiotis) Gieger, C. (Christian) Grönberg, H. (Henrik) Hattersley, A.T. (Andrew) Hengstenberg, C. (Christian) Hoffman, W. (Wolfgang) Lathrop, G.M. (Mark) Salomaa, V. (Veikko) Schreiber, S. (Stefan) Uda, M. (Manuela) Waterworth, D. (Dawn) Wright, A.F. (Alan) Assimes, T.L. (Themistocles) Barroso, I.E. (Inês) Hofman, A. (Albert) Mohlke, K.L. (Karen) Boomsma, D.I. (Dorret) Caulfield, M. (Mark) Cupples, L.A. (Adrienne) Fox, C.S. (Caroline) Gudnason, V. (Vilmundur) Gyllensten, U. (Ulf) Harris, T.B. (Tamara) Hayes, R.B. (Richard) Järvelin, M.R. Mooser, V. (Vincent) Munroe, P. (Patricia) Ouwehand, W.H. (Willem) Penninx, B.W.J.H. (Brenda) Pramstaller, P.P. (Peter Paul) Quertermous, T. (Thomas) Rudan, I. (Igor) Samani, N.J. (Nilesh) Spector, T.D. (Timothy) Völzke, H. (Henry) Watkins, H. (Hugh) Wilson, J.F. (James) Groop, L. (Leif) Haritunians, T. (Talin) Hu, F.B. (Frank) Metspalu, A. (Andres) North, K.E. (Kari) Schlessinger, D. Wareham, N.J. (Nick) Hunter, D.J. (David) O´Connell, J.R. Strachan, D.P. (David) Wichmann, H.E. (Heinz Erich) Borecki, I.B. (Ingrid) Duijn, C.M. (Cornelia) van Schadt, E.E. (Eric) Thorsteinsdottir, U. (Unnur) Peltonen, L. (Leena Johanna) Uitterlinden, A.G. (André) Visscher, P.M. (Peter) Chatterjee, N. (Nilanjan) Erdmann, J. (Jeanette) Loos, R.J.F. (Ruth) Boehnke, M. (Michael) McCarthy, M.I. (Mark) Ingelsson, E. (Erik) Lindgren, C.M. (Cecilia) Abecasis, G.R. (Gonçalo) Stefansson, K. (Kari) Frayling, T.M. (Timothy) Hirschhorn, J.N. (Joel) Ardlie, K.G. (Kristin) Weedon, M.N. (Michael) Allen, H.L. Estrada Gil, K. (Karol) Lettre, G. (Guillaume) Berndt, S.I. (Sonja) Rivadeneira Ramirez, F. (Fernando) Willer, C.J. (Cristen) Jackson, A.U. (Anne) Vedantam, S. (Sailaja) Raychaudhuri, S. (Soumya) Ferreira, T. (Teresa) Wood, A.R. (Andrew) Weyant, R.J. (Robert) Segrè, A.V. (Ayellet) Speliotes, E.K. (Elizabeth) Wheeler, E. (Eleanor) Soranzo, N. (Nicole) Park, J.H. Yang, J. (Joanna) Gudbjartsson, D.F. (Daniel) Heard-Costa, N.L. (Nancy) Randall, J.C. (Joshua) Qi, L. (Lu) Smith, A.V. (Albert Vernon) Mägi, R. (Reedik) Pastinen, T. (Tomi) Liang, L. (Liming) Heid, I.M. (Iris) Luan, J. Thorleifsson, G. (Gudmar) Winkler, T.W. (Thomas) Goddard, M.E. (Michael) Lo, K.S. Palmer, C. (Cameron) Workalemahu, T. (Tsegaselassie) Aulchenko, Y.S. (Yurii) Johansson, A. (Åsa) Zillikens, M.C. (Carola) Feitosa, M.F. (Mary Furlan) Esko, T. (Tõnu) Johnson, T. (Toby) Ketkar, S. (Shamika) Kraft, P. (Peter) Mangino, M. (Massimo) Prokopenko, I. (Inga) Absher, D. (Devin) Albrecht, E. (Eva) Ernst, F.D.J. (Florian) Glazer, N.L. (Nicole) Hayward, C. (Caroline) Hottenga, J.J. (Jouke Jan) Jacobs, K.B. (Kevin) Knowles, J.W. (Joshua) Kutalik, Z. (Zoltán) Monda, K.L. (Keri) Polasek, O. (Ozren) Preuss, M. (Michael) Rayner, N.W. (Nigel William) Robertson, N.R. (Neil) Steinthorsdottir, V. (Valgerdur) Tyrer, J.P. (Jonathan) Voight, B.F. (Benjamin) Wiklund, F. (Fredrik) Xu, J. (Jianfeng) Zhao, J.H. (Jing Hua) Nyholt, D.R. (Dale) Pellikka, N. (Niina) Perola, M. (Markus) Perry, J.R.B. (John) Surakka, I. (Ida) Tammesoo, M.L. Altmaier, E.L. (Elizabeth) Amin, N. (Najaf) Aspelund, T. (Thor) Bhangale, T. (Tushar) Boucher, G. (Gabrielle) Chasman, D.I. (Daniel) Chen, C. (Constance) Coin, L. (Lachlan) Cooper, M.N. (Matthew) Dixon, A.L. (Anna) Gibson, Q. (Quince) Grundberg, E. (Elin) Hao, K. (Ke) Junttila, M.J. (Juhani) Kaplan, R.C. (Robert) Kettunen, J. (Johannes) König, I.R. (Inke) Kwan, T. (Tony) Lawrence, R.W. (Robert) Levinson, D.F. (Douglas) Lorentzon, M. (Mattias) McKnight, B. (Barbara) Morris, A.D. (Andrew) Müller, M. (Martina) Ngwa, J.S. Purcell, S. (Shaun) Rafelt, S. (Suzanne) Salem, R.M. (Rany) Salvi, E. (Erika) Sanna, S. (Serena) Shi, J. (Jianxin) Sovio, U. (Ulla) Thompson, J.R. (John) Turchin, M.C. (Michael) Vandenput, L. (Liesbeth) Verlaan, D.J. (Dominique) Vitart, V. (Veronique) White, C.C. (Charles) Ziegler, A. (Andreas) Almgren, P. (Peter) Balmforth, A.J. (Anthony) Campbell, H. (Harry) Citterio, L. (Lorena) Grandi, A. (Alessandro) de Dominiczak, A. (Anna) Duan, J. (Jubao) Elliott, P. (Paul) Elosua, R. (Roberto) Eriksson, J.G. (Johan) Freimer, N.B. (Nelson) Geus, E.J.C. (Eco) de Glorioso, N. (Nicola) Haiqing, S. (Shen) Hartikainen, A.L. Havulinna, A.S. (Aki) Hicks, A.A. (Andrew) Hui, J. (Jennie) Igl, W. (Wilmar) Illig, T. (Thomas) Jula, A. (Antti) Kajantie, E. (Eero) Kilpeläinen, T.O. (Tuomas) Koiranen, M. (Markku) Kolcic, I. (Ivana) Koskinen, S. (Seppo) Kovacs, P. (Peter) Laitinen, J. (Jaana) Liu, J. (Jianjun) Lokki, M.L. Marusic, A. (Ana) Maschio, A. Meitinger, T. (Thomas) Mulas, A. (Antonella) Paré, G. (Guillaume) Parker, A.N. (Alex) Peden, J. (John) Petersmann, A. (Astrid) Pichler, I. (Irene) Pietilainen, K.H. (Kirsi Hannele) Pouta, A. (Anneli) Ridderstråle, M. (Martin) Rotter, J.I. (Jerome) Sambrook, J.G. (Jennifer) Sanders, A.R. (Alan) Schmidt, C.O. (Carsten Oliver) Sinisalo, J. (Juha) Smit, J.H. (Jan) Stringham, H.M. (Heather) Walters, G.B. (Bragi) Widen, E. (Elisabeth) Wild, S.H. (Sarah) Willemsen, G.A.H.M. (Gonneke) Zagato, L. (Laura) Zgaga, L. (Lina) Zitting, P. (Paavo) Alavere, H. (Helene) Farrall, M. (Martin) McArdle, W.L. (Wendy) Nelis, M. (Mari) Peters, M.J. (Marjolein) Ripatti, S. (Samuli) Meurs, J.B.J. (Joyce) van Aben, K.K.H. (Katja) Beckmann, J.S. (Jacques) Beilby, J.P. (John) Bergman, R.N. (Richard) Bergmann, S.M. (Sven) Collins, F.S. (Francis) Cusi, D. (Daniele) Heijer, M. (Martin) den Eiriksdottir, G. (Gudny) Gejman, P.V. (Pablo) Hall, A.S. (Alistair) Hamsten, A. (Anders) Huikuri, H.V. (Heikki) Iribarren, C. (Carlos) Kähönen, M. (Mika) Kaprio, J. (Jaakko) Kathiresan, S. (Sekar) Kiemeney, L.A.L.M. (Bart) Kocher, T. (Thomas) Launer, L.J. (Lenore) Lehtimäki, T. (Terho) Melander, O. (Olle) Mosley, T.H. (Thomas) Musk, A.W. (Arthur) Nieminen, M.S. (Markku) O'Donnell, C.J. (Christopher) Ohlsson, C. (Claes) Oostra, B.A. (Ben) Raitakari, O. (Olli) Ridker, P.M. (Paul) Rioux, J.D. (John) Rissanen, A. (Aila) Rivolta, C. (Carlo) Schunkert, H. (Heribert) Shuldiner, A.R. (Alan) Siscovick, D.S. (David) Stumvoll, M. (Michael) Tönjes, A. (Anke) Tuomilehto, J. (Jaakko) Ommen, G.J. (Gert) van Viikari, J. (Jorma) Heath, A.C. (Andrew) Martin, N.G. (Nicholas) Montgomery, G.W. (Grant) Province, M.A. (Mike) Kayser, M.H. (Manfred) Arnold, A.M. (Alice) Atwood, L.D. (Larry) Boerwinkle, E.A. (Eric) Chanock, S.J. (Stephen) Deloukas, P. (Panagiotis) Gieger, C. (Christian) Grönberg, H. (Henrik) Hattersley, A.T. (Andrew) Hengstenberg, C. (Christian) Hoffman, W. (Wolfgang) Lathrop, G.M. (Mark) Salomaa, V. (Veikko) Schreiber, S. (Stefan) Uda, M. (Manuela) Waterworth, D. (Dawn) Wright, A.F. (Alan) Assimes, T.L. (Themistocles) Barroso, I.E. (Inês) Hofman, A. (Albert) Mohlke, K.L. (Karen) Boomsma, D.I. (Dorret) Caulfield, M. (Mark) Cupples, L.A. (Adrienne) Fox, C.S. (Caroline) Gudnason, V. (Vilmundur) Gyllensten, U. (Ulf) Harris, T.B. (Tamara) Hayes, R.B. (Richard) Järvelin, M.R. Mooser, V. (Vincent) Munroe, P. (Patricia) Ouwehand, W.H. (Willem) Penninx, B.W.J.H. (Brenda) Pramstaller, P.P. (Peter Paul) Quertermous, T. (Thomas) Rudan, I. (Igor) Samani, N.J. (Nilesh) Spector, T.D. (Timothy) Völzke, H. (Henry) Watkins, H. (Hugh) Wilson, J.F. (James) Groop, L. (Leif) Haritunians, T. (Talin) Hu, F.B. (Frank) Metspalu, A. (Andres) North, K.E. (Kari) Schlessinger, D. Wareham, N.J. (Nick) Hunter, D.J. (David) O´Connell, J.R. Strachan, D.P. (David) Wichmann, H.E. (Heinz Erich) Borecki, I.B. (Ingrid) Duijn, C.M. (Cornelia) van Schadt, E.E. (Eric) Thorsteinsdottir, U. (Unnur) Peltonen, L. (Leena Johanna) Uitterlinden, A.G. (André) Visscher, P.M. (Peter) Chatterjee, N. (Nilanjan) Erdmann, J. (Jeanette) Loos, R.J.F. (Ruth) Boehnke, M. (Michael) McCarthy, M.I. (Mark) Ingelsson, E. (Erik) Lindgren, C.M. (Cecilia) Abecasis, G.R. (Gonçalo) Stefansson, K. (Kari) Frayling, T.M. (Timothy) Hirschhorn, J.N. (Joel) Ardlie, K.G. (Kristin) Weedon, M.N. (Michael)
Publication Year :
2010
Abstract
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P<0.001). Second, the likely causal gene is often located near the most str
Details
Database :
OAIster
Notes :
Nature: international weekly journal of science vol. 467 no. 7317, pp. 832-838, English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn929962628
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.nature09410