Hundreds of variants clustered in genomic loci and biological pathways affect human height

Hana Lango Allen; Karol Estrada; Guillaume Lettre; Sonja I. Berndt; Michael N. Weedon; Fernando Rivadeneira; Cristen J. Willer; Anne U. Jackson; Sailaja Vedantam; Soumya Raychaudhuri; Teresa Ferreira; Andrew R. Wood; Robert J. Weyant; Ayellet V. Segrè; Elizabeth K. Speliotes; Eleanor Wheeler; Nicole Soranzo; Ju Hyun Park; Jian Yang; Daniel Gudbjartsson; Nancy L. Heard-Costa; Joshua C. Randall; Lu Qi; Albert Vernon Smith; Reedik Mägi; Tomi Pastinen; Liming Liang; Iris M. Heid; Jian'An Luan; Gudmar Thorleifsson; Thomas W. Winkler; Michael E. Goddard; Ken Sin Lo; Cameron Palmer; Tsegaselassie Workalemahu; Yurii S. Aulchenko; Åsa Johansson; M. Carola Zillikens; Mary F. Feitosa; Toñu Esko; Toby Johnson; Shamika Ketkar; Peter Kraft; Massimo Mangino; Inga Prokopenko; Devin Absher; Eva Albrecht; Florian Ernst; Nicole L. Glazer; Caroline Hayward; Jouke Jan Hottenga; Kevin B. Jacobs; Joshua W. Knowles; Zoltán Kutalik; Keri L. Monda; Ozren Polasek; Michael Preuss; Nigel W. Rayner; Neil R. Robertson; Valgerdur Steinthorsdottir; Jonathan P. Tyrer; Benjamin F. Voight; Fredrik Wiklund; Jianfeng Xu; Jing Hua Zhao; Dale R. Nyholt; Niina Pellikka; Markus Perola; John B. Perry; Ida Surakka; Mari Liis Tammesoo; Elizabeth L. Altmaier; Najaf Amin; Thor Aspelund; Tushar Bhangale; Gabrielle Boucher; Daniel I. Chasman; Constance Chen; Lachlan Coin; Matthew N. Cooper; Anna L. Dixon; Quince Gibson; Elin Grundberg; Ke Hao; M. Juhani Junttila; Lee M. Kaplan; Johannes Kettunen; Inke R. König; Tony Kwan; Robert W. Lawrence; Douglas F. Levinson; Mattias Lorentzon; Barbara McKnight; Martina Müller; Julius Suh Ngwa; Shaun Purcell; Suzanne Rafelt; Rany M. Salem; Erika Salvi; Serena Sanna; Jianxin Shi; Ulla Sovio; John R. Thompson; Michael C. Turchin; Liesbeth Vandenput; Dominique J. Verlaan; Veronique Vitart; Charles C. White; Andreas Ziegler; Peter Almgren; Anthony J. Balmforth; Harry Campbell; Lorena Citterio; Alessandro De Grandi; Anna Dominiczak; Jubao Duan; Paul Elliott; Roberto Elosua; Johan G. Eriksson; Nelson B. Freimer; Eco J C Geus; Nicola Glorioso; Shen Haiqing; Anna Liisa Hartikainen; Aki S. Havulinna; Andrew A. Hicks; Jennie Hui; Wilmar Igl; Thomas Illig; Antti Jula; Eero Kajantie; Tuomas O. Kilpeläinen; Markku Koiranen; Ivana Kolcic; Seppo Koskinen; Peter Kovacs; Jaana Laitinen; Jianjun Liu; Marja Liisa Lokki; Ana Marusic; Andrea Maschio; Thomas Meitinger; Antonella Mulas; Guillaume Paré; Alex N. Parker; John F. Peden; Astrid Petersmann; Irene Pichler; Kirsi H. Pietiläinen; Anneli Pouta; Martin Ridderstråle; Jerome I. Rotter; Jennifer G. Sambrook; Alan R. Sanders; Carsten Oliver Schmidt; Juha Sinisalo; Jan H. Smit; Heather M. Stringham; G. Bragi Walters; Elisabeth Widen; Sarah H. Wild; Gonneke Willemsen; Laura Zagato; Lina Zgaga; Paavo Zitting; Helene Alavere; Martin Farrall; Wendy L. McArdle; Mari Nelis; Marjolein J. Peters; Samuli Ripatti; Joyce B J Van Meurs; Katja K. Aben; Kristin G. Ardlie; Jacques S. Beckmann; John P. Beilby; Richard N. Bergman; Sven Bergmann; Francis S. Collins; Daniele Cusi; Martin Den Heijer; Gudny Eiriksdottir; Pablo V. Gejman; Alistair S. Hall; Anders Hamsten; Heikki V. Huikuri; Carlos Iribarren; Mika Kähönen; Jaakko Kaprio; Sekar Kathiresan; Lambertus Kiemeney; Thomas Kocher; Lenore J. Launer; Terho Lehtimäki; Olle Melander; Tom H. Mosley; Arthur W. Musk; Markku S. Nieminen; Christopher J. O'Donnell; Claes Ohlsson; Ben Oostra; Lyle J. Palmer; Olli Raitakari; Paul M. Ridker; John D. Rioux; Aila Rissanen; Carlo Rivolta; Heribert Schunkert; Alan R. Shuldiner; David S. Siscovick; Michael Stumvoll; Anke Tönjes; Jaakko Tuomilehto; Gert Jan Van Ommen; Jorma Viikari; Andrew C. Heath; Nicholas G. Martin; Grant W. Montgomery; Michael A. Province; Manfred Kayser; Alice M. Arnold; Larry D.Atwood; Eric Boerwinkle; Stephen J. Chanock; Panos Deloukas; Christian Gieger; Henrik Grönberg; Per Hall; Andrew T. Hattersley; Christian Hengstenberg; Wolfgang Hoffman; G. Mark Lathrop; Veikko Salomaa; Stefan Schreiber; Manuela Uda; Dawn Waterworth; Alan F. Wright; Themistocles L. Assimes; Inês Barroso; Albert Hofman; Karen L. Mohlke; Dorret I. Boomsma; Mark J. Caulfield; L. Adrienne Cupples; Jeanette Erdmann; Caroline S. Fox; Vilmundur Gudnason; Ulf Gyllensten; Tamara B. Harris; Richard B. Hayes; Marjo Riitta Jarvelin; Vincent Mooser; Patricia B. Munroe; Willem H. Ouwehand; Brenda W. Penninx; Peter P. Pramstaller; Thomas Quertermous; Igor Rudan; Nilesh J. Samani; Timothy D. Spector; Henry Völzke; Hugh Watkins; James F. Wilson; Leif C. Groop; Talin Haritunians; Frank B. Hu; Robert C. Kaplan; Andres Metspalu; Kari E. North; David Schlessinger; Nicholas J. Wareham; David J. Hunter; Jeffrey R. O'Connell; David P. Strachan; H. Erich Wichmann; Ingrid B. Borecki; Cornelia M. Van Duijn; Eric E. Schadt; Unnur Thorsteinsdottir; Leena Peltonen; André G. Uitterlinden; Peter M. Visscher; Nilanjan Chatterjee; Ruth J F Loos; Michael Boehnke; Mark I. McCarthy; Erik Ingelsson; Cecilia M. Lindgren; Gonçalo R. Abecasis; Kari Stefansson; Timothy M. Frayling; Joel N. Hirschhorn; Andrew Morris

doi:10.1038/nature09410

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Hana Lango Allen, Karol Estrada, Guillaume Lettre, Sonja I. Berndt, Michael N. Weedon, Fernando Rivadeneira, Cristen J. Willer, Anne U. Jackson, Sailaja Vedantam, Soumya Raychaudhuri, Teresa Ferreira, Andrew R. Wood, Robert J. Weyant, Ayellet V. Segrè, Elizabeth K. Speliotes, Eleanor Wheeler, Nicole Soranzo, Ju Hyun Park, Jian Yang, Daniel GudbjartssonNancy L. Heard-Costa, Joshua C. Randall, Lu Qi, Albert Vernon Smith, Reedik Mägi, Tomi Pastinen, Liming Liang, Iris M. Heid, Jian'An Luan, Gudmar Thorleifsson, Thomas W. Winkler, Michael E. Goddard, Ken Sin Lo, Cameron Palmer, Tsegaselassie Workalemahu, Yurii S. Aulchenko, Åsa Johansson, M. Carola Zillikens, Mary F. Feitosa, Toñu Esko, Toby Johnson, Shamika Ketkar, Peter Kraft, Massimo Mangino, Inga Prokopenko, Devin Absher, Eva Albrecht, Florian Ernst, Nicole L. Glazer, Caroline Hayward, Jouke Jan Hottenga, Kevin B. Jacobs, Joshua W. Knowles, Zoltán Kutalik, Keri L. Monda, Ozren Polasek, Michael Preuss, Nigel W. Rayner, Neil R. Robertson, Valgerdur Steinthorsdottir, Jonathan P. Tyrer, Benjamin F. Voight, Fredrik Wiklund, Jianfeng Xu, Jing Hua Zhao, Dale R. Nyholt, Niina Pellikka, Markus Perola, John B. Perry, Ida Surakka, Mari Liis Tammesoo, Elizabeth L. Altmaier, Najaf Amin, Thor Aspelund, Tushar Bhangale, Gabrielle Boucher, Daniel I. Chasman, Constance Chen, Lachlan Coin, Matthew N. Cooper, Anna L. Dixon, Quince Gibson, Elin Grundberg, Ke Hao, M. Juhani Junttila, Lee M. Kaplan, Johannes Kettunen, Inke R. König, Tony Kwan, Robert W. Lawrence, Douglas F. Levinson, Mattias Lorentzon, Barbara McKnight, Martina Müller, Julius Suh Ngwa, Shaun Purcell, Suzanne Rafelt, Rany M. Salem, Erika Salvi, Serena Sanna, Jianxin Shi, Ulla Sovio, John R. Thompson, Michael C. Turchin, Liesbeth Vandenput, Dominique J. Verlaan, Veronique Vitart, Charles C. White, Andreas Ziegler, Peter Almgren, Anthony J. Balmforth, Harry Campbell, Lorena Citterio, Alessandro De Grandi, Anna Dominiczak, Jubao Duan, Paul Elliott, Roberto Elosua, Johan G. Eriksson, Nelson B. Freimer, Eco J C Geus, Nicola Glorioso, Shen Haiqing, Anna Liisa Hartikainen, Aki S. Havulinna, Andrew A. Hicks, Jennie Hui, Wilmar Igl, Thomas Illig, Antti Jula, Eero Kajantie, Tuomas O. Kilpeläinen, Markku Koiranen, Ivana Kolcic, Seppo Koskinen, Peter Kovacs, Jaana Laitinen, Jianjun Liu, Marja Liisa Lokki, Ana Marusic, Andrea Maschio, Thomas Meitinger, Antonella Mulas, Guillaume Paré, Alex N. Parker, John F. Peden, Astrid Petersmann, Irene Pichler, Kirsi H. Pietiläinen, Anneli Pouta, Martin Ridderstråle, Jerome I. Rotter, Jennifer G. Sambrook, Alan R. Sanders, Carsten Oliver Schmidt, Juha Sinisalo, Jan H. Smit, Heather M. Stringham, G. Bragi Walters, Elisabeth Widen, Sarah H. Wild, Gonneke Willemsen, Laura Zagato, Lina Zgaga, Paavo Zitting, Helene Alavere, Martin Farrall, Wendy L. McArdle, Mari Nelis, Marjolein J. Peters, Samuli Ripatti, Joyce B J Van Meurs, Katja K. Aben, Kristin G. Ardlie, Jacques S. Beckmann, John P. Beilby, Richard N. Bergman, Sven Bergmann, Francis S. Collins, Daniele Cusi, Martin Den Heijer, Gudny Eiriksdottir, Pablo V. Gejman, Alistair S. Hall, Anders Hamsten, Heikki V. Huikuri, Carlos Iribarren, Mika Kähönen, Jaakko Kaprio, Sekar Kathiresan, Lambertus Kiemeney, Thomas Kocher, Lenore J. Launer, Terho Lehtimäki, Olle Melander, Tom H. Mosley, Arthur W. Musk, Markku S. Nieminen, Christopher J. O'Donnell, Claes Ohlsson, Ben Oostra, Lyle J. Palmer, Olli Raitakari, Paul M. Ridker, John D. Rioux, Aila Rissanen, Carlo Rivolta, Heribert Schunkert, Alan R. Shuldiner, David S. Siscovick, Michael Stumvoll, Anke Tönjes, Jaakko Tuomilehto, Gert Jan Van Ommen, Jorma Viikari, Andrew C. Heath, Nicholas G. Martin, Grant W. Montgomery, Michael A. Province, Manfred Kayser, Alice M. Arnold, Larry D.Atwood, Eric Boerwinkle, Stephen J. Chanock, Panos Deloukas, Christian Gieger, Henrik Grönberg, Per Hall, Andrew T. Hattersley, Christian Hengstenberg, Wolfgang Hoffman, G. Mark Lathrop, Veikko Salomaa, Stefan Schreiber, Manuela Uda, Dawn Waterworth, Alan F. Wright, Themistocles L. Assimes, Inês Barroso, Albert Hofman, Karen L. Mohlke, Dorret I. Boomsma, Mark J. Caulfield, L. Adrienne Cupples, Jeanette Erdmann, Caroline S. Fox, Vilmundur Gudnason, Ulf Gyllensten, Tamara B. Harris, Richard B. Hayes, Marjo Riitta Jarvelin, Vincent Mooser, Patricia B. Munroe, Willem H. Ouwehand, Brenda W. Penninx, Peter P. Pramstaller, Thomas Quertermous, Igor Rudan, Nilesh J. Samani, Timothy D. Spector, Henry Völzke, Hugh Watkins, James F. Wilson, Leif C. Groop, Talin Haritunians, Frank B. Hu, Robert C. Kaplan, Andres Metspalu, Kari E. North, David Schlessinger, Nicholas J. Wareham, David J. Hunter, Jeffrey R. O'Connell, David P. Strachan, H. Erich Wichmann, Ingrid B. Borecki, Cornelia M. Van Duijn, Eric E. Schadt, Unnur Thorsteinsdottir, Leena Peltonen, André G. Uitterlinden, Peter M. Visscher, Nilanjan Chatterjee, Ruth J F Loos, Michael Boehnke, Mark I. McCarthy, Erik Ingelsson, Cecilia M. Lindgren, Gonçalo R. Abecasis, Kari Stefansson, Timothy M. Frayling, Joel N. Hirschhorn, Andrew Morris

University of Bath

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	832-838
Number of pages	6
Journal	Nature
Volume	467
Issue number	7317
DOIs	https://doi.org/10.1038/nature09410
Publication status	Published - 14 Oct 2010

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10.1038/nature09410

Cite this

Allen, H. L., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., Ferreira, T., Wood, A. R., Weyant, R. J., Segrè, A. V., Speliotes, E. K., Wheeler, E., Soranzo, N., Park, J. H., Yang, J., ... Morris, A. (2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature, 467(7317), 832-838. https://doi.org/10.1038/nature09410

@article{eab8adc9a7ad458ba0e8b4c7d9044bf4,

title = "Hundreds of variants clustered in genomic loci and biological pathways affect human height",

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",

author = "Allen, {Hana Lango} and Karol Estrada and Guillaume Lettre and Berndt, {Sonja I.} and Weedon, {Michael N.} and Fernando Rivadeneira and Willer, {Cristen J.} and Jackson, {Anne U.} and Sailaja Vedantam and Soumya Raychaudhuri and Teresa Ferreira and Wood, {Andrew R.} and Weyant, {Robert J.} and Segr{\`e}, {Ayellet V.} and Speliotes, {Elizabeth K.} and Eleanor Wheeler and Nicole Soranzo and Park, {Ju Hyun} and Jian Yang and Daniel Gudbjartsson and Heard-Costa, {Nancy L.} and Randall, {Joshua C.} and Lu Qi and Smith, {Albert Vernon} and Reedik M{\"a}gi and Tomi Pastinen and Liming Liang and Heid, {Iris M.} and Jian'An Luan and Gudmar Thorleifsson and Winkler, {Thomas W.} and Goddard, {Michael E.} and Lo, {Ken Sin} and Cameron Palmer and Tsegaselassie Workalemahu and Aulchenko, {Yurii S.} and {\AA}sa Johansson and Zillikens, {M. Carola} and Feitosa, {Mary F.} and To{\~n}u Esko and Toby Johnson and Shamika Ketkar and Peter Kraft and Massimo Mangino and Inga Prokopenko and Devin Absher and Eva Albrecht and Florian Ernst and Glazer, {Nicole L.} and Caroline Hayward and Hottenga, {Jouke Jan} and Jacobs, {Kevin B.} and Knowles, {Joshua W.} and Zolt{\'a}n Kutalik and Monda, {Keri L.} and Ozren Polasek and Michael Preuss and Rayner, {Nigel W.} and Robertson, {Neil R.} and Valgerdur Steinthorsdottir and Tyrer, {Jonathan P.} and Voight, {Benjamin F.} and Fredrik Wiklund and Jianfeng Xu and Zhao, {Jing Hua} and Nyholt, {Dale R.} and Niina Pellikka and Markus Perola and Perry, {John B.} and Ida Surakka and Tammesoo, {Mari Liis} and Altmaier, {Elizabeth L.} and Najaf Amin and Thor Aspelund and Tushar Bhangale and Gabrielle Boucher and Chasman, {Daniel I.} and Constance Chen and Lachlan Coin and Cooper, {Matthew N.} and Dixon, {Anna L.} and Quince Gibson and Elin Grundberg and Ke Hao and Junttila, {M. Juhani} and Kaplan, {Lee M.} and Johannes Kettunen and K{\"o}nig, {Inke R.} and Tony Kwan and Lawrence, {Robert W.} and Levinson, {Douglas F.} and Mattias Lorentzon and Barbara McKnight and Martina M{\"u}ller and Ngwa, {Julius Suh} and Shaun Purcell and Suzanne Rafelt and Salem, {Rany M.} and Erika Salvi and Serena Sanna and Jianxin Shi and Ulla Sovio and Thompson, {John R.} and Turchin, {Michael C.} and Liesbeth Vandenput and Verlaan, {Dominique J.} and Veronique Vitart and White, {Charles C.} and Andreas Ziegler and Peter Almgren and Balmforth, {Anthony J.} and Harry Campbell and Lorena Citterio and {De Grandi}, Alessandro and Anna Dominiczak and Jubao Duan and Paul Elliott and Roberto Elosua and Eriksson, {Johan G.} and Freimer, {Nelson B.} and Geus, {Eco J C} and Nicola Glorioso and Shen Haiqing and Hartikainen, {Anna Liisa} and Havulinna, {Aki S.} and Hicks, {Andrew A.} and Jennie Hui and Wilmar Igl and Thomas Illig and Antti Jula and Eero Kajantie and Kilpel{\"a}inen, {Tuomas O.} and Markku Koiranen and Ivana Kolcic and Seppo Koskinen and Peter Kovacs and Jaana Laitinen and Jianjun Liu and Lokki, {Marja Liisa} and Ana Marusic and Andrea Maschio and Thomas Meitinger and Antonella Mulas and Guillaume Par{\'e} and Parker, {Alex N.} and Peden, {John F.} and Astrid Petersmann and Irene Pichler and Pietil{\"a}inen, {Kirsi H.} and Anneli Pouta and Martin Ridderstr{\aa}le and Rotter, {Jerome I.} and Sambrook, {Jennifer G.} and Sanders, {Alan R.} and Schmidt, {Carsten Oliver} and Juha Sinisalo and Smit, {Jan H.} and Stringham, {Heather M.} and Walters, {G. Bragi} and Elisabeth Widen and Wild, {Sarah H.} and Gonneke Willemsen and Laura Zagato and Lina Zgaga and Paavo Zitting and Helene Alavere and Martin Farrall and McArdle, {Wendy L.} and Mari Nelis and Peters, {Marjolein J.} and Samuli Ripatti and {Van Meurs}, {Joyce B J} and Aben, {Katja K.} and Ardlie, {Kristin G.} and Beckmann, {Jacques S.} and Beilby, {John P.} and Bergman, {Richard N.} and Sven Bergmann and Collins, {Francis S.} and Daniele Cusi and {Den Heijer}, Martin and Gudny Eiriksdottir and Gejman, {Pablo V.} and Hall, {Alistair S.} and Anders Hamsten and Huikuri, {Heikki V.} and Carlos Iribarren and Mika K{\"a}h{\"o}nen and Jaakko Kaprio and Sekar Kathiresan and Lambertus Kiemeney and Thomas Kocher and Launer, {Lenore J.} and Terho Lehtim{\"a}ki and Olle Melander and Mosley, {Tom H.} and Musk, {Arthur W.} and Nieminen, {Markku S.} and O'Donnell, {Christopher J.} and Claes Ohlsson and Ben Oostra and Palmer, {Lyle J.} and Olli Raitakari and Ridker, {Paul M.} and Rioux, {John D.} and Aila Rissanen and Carlo Rivolta and Heribert Schunkert and Shuldiner, {Alan R.} and Siscovick, {David S.} and Michael Stumvoll and Anke T{\"o}njes and Jaakko Tuomilehto and {Van Ommen}, {Gert Jan} and Jorma Viikari and Heath, {Andrew C.} and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Province, {Michael A.} and Manfred Kayser and Arnold, {Alice M.} and Larry D.Atwood and Eric Boerwinkle and Chanock, {Stephen J.} and Panos Deloukas and Christian Gieger and Henrik Gr{\"o}nberg and Per Hall and Hattersley, {Andrew T.} and Christian Hengstenberg and Wolfgang Hoffman and Lathrop, {G. Mark} and Veikko Salomaa and Stefan Schreiber and Manuela Uda and Dawn Waterworth and Wright, {Alan F.} and Assimes, {Themistocles L.} and In{\^e}s Barroso and Albert Hofman and Mohlke, {Karen L.} and Boomsma, {Dorret I.} and Caulfield, {Mark J.} and Cupples, {L. Adrienne} and Jeanette Erdmann and Fox, {Caroline S.} and Vilmundur Gudnason and Ulf Gyllensten and Harris, {Tamara B.} and Hayes, {Richard B.} and Jarvelin, {Marjo Riitta} and Vincent Mooser and Munroe, {Patricia B.} and Ouwehand, {Willem H.} and Penninx, {Brenda W.} and Pramstaller, {Peter P.} and Thomas Quertermous and Igor Rudan and Samani, {Nilesh J.} and Spector, {Timothy D.} and Henry V{\"o}lzke and Hugh Watkins and Wilson, {James F.} and Groop, {Leif C.} and Talin Haritunians and Hu, {Frank B.} and Kaplan, {Robert C.} and Andres Metspalu and North, {Kari E.} and David Schlessinger and Wareham, {Nicholas J.} and Hunter, {David J.} and O'Connell, {Jeffrey R.} and Strachan, {David P.} and Wichmann, {H. Erich} and Borecki, {Ingrid B.} and {Van Duijn}, {Cornelia M.} and Schadt, {Eric E.} and Unnur Thorsteinsdottir and Leena Peltonen and Uitterlinden, {Andr{\'e} G.} and Visscher, {Peter M.} and Nilanjan Chatterjee and Loos, {Ruth J F} and Michael Boehnke and McCarthy, {Mark I.} and Erik Ingelsson and Lindgren, {Cecilia M.} and Abecasis, {Gon{\c c}alo R.} and Kari Stefansson and Frayling, {Timothy M.} and Hirschhorn, {Joel N.} and Andrew Morris",

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Research UK, United Kingdom",

year = "2010",

month = oct,

day = "14",

doi = "10.1038/nature09410",

language = "English",

volume = "467",

pages = "832--838",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7317",

}

Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segrè, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, JH, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Mägi, R, Pastinen, T, Liang, L, Heid, IM, Luan, JA, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, Å, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, JJ, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JB, Surakka, I, Tammesoo, ML, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, König, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Müller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, AL, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpeläinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, ML, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Paré, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietiläinen, KH, Pouta, A, Ridderstråle, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, Van Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, Den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kähönen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimäki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Tönjes, A, Tuomilehto, J, Van Ommen, GJ, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, D.Atwood, L, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Grönberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, MR, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Völzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Wichmann, HE, Borecki, IB, Van Duijn, CM, Schadt, EE, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, Hirschhorn, JN & Morris, A 2010, 'Hundreds of variants clustered in genomic loci and biological pathways affect human height', Nature, vol. 467, no. 7317, pp. 832-838. https://doi.org/10.1038/nature09410

TY - JOUR

T1 - Hundreds of variants clustered in genomic loci and biological pathways affect human height

AU - Allen, Hana Lango

AU - Estrada, Karol

AU - Lettre, Guillaume

AU - Berndt, Sonja I.

AU - Weedon, Michael N.

AU - Rivadeneira, Fernando

AU - Willer, Cristen J.

AU - Jackson, Anne U.

AU - Vedantam, Sailaja

AU - Raychaudhuri, Soumya

AU - Ferreira, Teresa

AU - Wood, Andrew R.

AU - Weyant, Robert J.

AU - Segrè, Ayellet V.

AU - Speliotes, Elizabeth K.

AU - Wheeler, Eleanor

AU - Soranzo, Nicole

AU - Park, Ju Hyun

AU - Yang, Jian

AU - Gudbjartsson, Daniel

AU - Heard-Costa, Nancy L.

AU - Randall, Joshua C.

AU - Qi, Lu

AU - Smith, Albert Vernon

AU - Mägi, Reedik

AU - Pastinen, Tomi

AU - Liang, Liming

AU - Heid, Iris M.

AU - Luan, Jian'An

AU - Thorleifsson, Gudmar

AU - Winkler, Thomas W.

AU - Goddard, Michael E.

AU - Lo, Ken Sin

AU - Palmer, Cameron

AU - Workalemahu, Tsegaselassie

AU - Aulchenko, Yurii S.

AU - Johansson, Åsa

AU - Zillikens, M. Carola

AU - Feitosa, Mary F.

AU - Esko, Toñu

AU - Johnson, Toby

AU - Ketkar, Shamika

AU - Kraft, Peter

AU - Mangino, Massimo

AU - Prokopenko, Inga

AU - Absher, Devin

AU - Albrecht, Eva

AU - Ernst, Florian

AU - Glazer, Nicole L.

AU - Hayward, Caroline

AU - Hottenga, Jouke Jan

AU - Jacobs, Kevin B.

AU - Knowles, Joshua W.

AU - Kutalik, Zoltán

AU - Monda, Keri L.

AU - Polasek, Ozren

AU - Preuss, Michael

AU - Rayner, Nigel W.

AU - Robertson, Neil R.

AU - Steinthorsdottir, Valgerdur

AU - Tyrer, Jonathan P.

AU - Voight, Benjamin F.

AU - Wiklund, Fredrik

AU - Xu, Jianfeng

AU - Zhao, Jing Hua

AU - Nyholt, Dale R.

AU - Pellikka, Niina

AU - Perola, Markus

AU - Perry, John B.

AU - Surakka, Ida

AU - Tammesoo, Mari Liis

AU - Altmaier, Elizabeth L.

AU - Amin, Najaf

AU - Aspelund, Thor

AU - Bhangale, Tushar

AU - Boucher, Gabrielle

AU - Chasman, Daniel I.

AU - Chen, Constance

AU - Coin, Lachlan

AU - Cooper, Matthew N.

AU - Dixon, Anna L.

AU - Gibson, Quince

AU - Grundberg, Elin

AU - Hao, Ke

AU - Junttila, M. Juhani

AU - Kaplan, Lee M.

AU - Kettunen, Johannes

AU - König, Inke R.

AU - Kwan, Tony

AU - Lawrence, Robert W.

AU - Levinson, Douglas F.

AU - Lorentzon, Mattias

AU - McKnight, Barbara

AU - Müller, Martina

AU - Ngwa, Julius Suh

AU - Purcell, Shaun

AU - Rafelt, Suzanne

AU - Salem, Rany M.

AU - Salvi, Erika

AU - Sanna, Serena

AU - Shi, Jianxin

AU - Sovio, Ulla

AU - Thompson, John R.

AU - Turchin, Michael C.

AU - Vandenput, Liesbeth

AU - Verlaan, Dominique J.

AU - Vitart, Veronique

AU - White, Charles C.

AU - Ziegler, Andreas

AU - Almgren, Peter

AU - Balmforth, Anthony J.

AU - Campbell, Harry

AU - Citterio, Lorena

AU - De Grandi, Alessandro

AU - Dominiczak, Anna

AU - Duan, Jubao

AU - Elliott, Paul

AU - Elosua, Roberto

AU - Eriksson, Johan G.

AU - Freimer, Nelson B.

AU - Geus, Eco J C

AU - Glorioso, Nicola

AU - Haiqing, Shen

AU - Hartikainen, Anna Liisa

AU - Havulinna, Aki S.

AU - Hicks, Andrew A.

AU - Hui, Jennie

AU - Igl, Wilmar

AU - Illig, Thomas

AU - Jula, Antti

AU - Kajantie, Eero

AU - Kilpeläinen, Tuomas O.

AU - Koiranen, Markku

AU - Kolcic, Ivana

AU - Koskinen, Seppo

AU - Kovacs, Peter

AU - Laitinen, Jaana

AU - Liu, Jianjun

AU - Lokki, Marja Liisa

AU - Marusic, Ana

AU - Maschio, Andrea

AU - Meitinger, Thomas

AU - Mulas, Antonella

AU - Paré, Guillaume

AU - Parker, Alex N.

AU - Peden, John F.

AU - Petersmann, Astrid

AU - Pichler, Irene

AU - Pietiläinen, Kirsi H.

AU - Pouta, Anneli

AU - Ridderstråle, Martin

AU - Rotter, Jerome I.

AU - Sambrook, Jennifer G.

AU - Sanders, Alan R.

AU - Schmidt, Carsten Oliver

AU - Sinisalo, Juha

AU - Smit, Jan H.

AU - Stringham, Heather M.

AU - Walters, G. Bragi

AU - Widen, Elisabeth

AU - Wild, Sarah H.

AU - Willemsen, Gonneke

AU - Zagato, Laura

AU - Zgaga, Lina

AU - Zitting, Paavo

AU - Alavere, Helene

AU - Farrall, Martin

AU - McArdle, Wendy L.

AU - Nelis, Mari

AU - Peters, Marjolein J.

AU - Ripatti, Samuli

AU - Van Meurs, Joyce B J

AU - Aben, Katja K.

AU - Ardlie, Kristin G.

AU - Beckmann, Jacques S.

AU - Beilby, John P.

AU - Bergman, Richard N.

AU - Bergmann, Sven

AU - Collins, Francis S.

AU - Cusi, Daniele

AU - Den Heijer, Martin

AU - Eiriksdottir, Gudny

AU - Gejman, Pablo V.

AU - Hall, Alistair S.

AU - Hamsten, Anders

AU - Huikuri, Heikki V.

AU - Iribarren, Carlos

AU - Kähönen, Mika

AU - Kaprio, Jaakko

AU - Kathiresan, Sekar

AU - Kiemeney, Lambertus

AU - Kocher, Thomas

AU - Launer, Lenore J.

AU - Lehtimäki, Terho

AU - Melander, Olle

AU - Mosley, Tom H.

AU - Musk, Arthur W.

AU - Nieminen, Markku S.

AU - O'Donnell, Christopher J.

AU - Ohlsson, Claes

AU - Oostra, Ben

AU - Palmer, Lyle J.

AU - Raitakari, Olli

AU - Ridker, Paul M.

AU - Rioux, John D.

AU - Rissanen, Aila

AU - Rivolta, Carlo

AU - Schunkert, Heribert

AU - Shuldiner, Alan R.

AU - Siscovick, David S.

AU - Stumvoll, Michael

AU - Tönjes, Anke

AU - Tuomilehto, Jaakko

AU - Van Ommen, Gert Jan

AU - Viikari, Jorma

AU - Heath, Andrew C.

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Province, Michael A.

AU - Kayser, Manfred

AU - Arnold, Alice M.

AU - D.Atwood, Larry

AU - Boerwinkle, Eric

AU - Chanock, Stephen J.

AU - Deloukas, Panos

AU - Gieger, Christian

AU - Grönberg, Henrik

AU - Hall, Per

AU - Hattersley, Andrew T.

AU - Hengstenberg, Christian

AU - Hoffman, Wolfgang

AU - Lathrop, G. Mark

AU - Salomaa, Veikko

AU - Schreiber, Stefan

AU - Uda, Manuela

AU - Waterworth, Dawn

AU - Wright, Alan F.

AU - Assimes, Themistocles L.

AU - Barroso, Inês

AU - Hofman, Albert

AU - Mohlke, Karen L.

AU - Boomsma, Dorret I.

AU - Caulfield, Mark J.

AU - Cupples, L. Adrienne

AU - Erdmann, Jeanette

AU - Fox, Caroline S.

AU - Gudnason, Vilmundur

AU - Gyllensten, Ulf

AU - Harris, Tamara B.

AU - Hayes, Richard B.

AU - Jarvelin, Marjo Riitta

AU - Mooser, Vincent

AU - Munroe, Patricia B.

AU - Ouwehand, Willem H.

AU - Penninx, Brenda W.

AU - Pramstaller, Peter P.

AU - Quertermous, Thomas

AU - Rudan, Igor

AU - Samani, Nilesh J.

AU - Spector, Timothy D.

AU - Völzke, Henry

AU - Watkins, Hugh

AU - Wilson, James F.

AU - Groop, Leif C.

AU - Haritunians, Talin

AU - Hu, Frank B.

AU - Kaplan, Robert C.

AU - Metspalu, Andres

AU - North, Kari E.

AU - Schlessinger, David

AU - Wareham, Nicholas J.

AU - Hunter, David J.

AU - O'Connell, Jeffrey R.

AU - Strachan, David P.

AU - Wichmann, H. Erich

AU - Borecki, Ingrid B.

AU - Van Duijn, Cornelia M.

AU - Schadt, Eric E.

AU - Thorsteinsdottir, Unnur

AU - Peltonen, Leena

AU - Uitterlinden, André G.

AU - Visscher, Peter M.

AU - Chatterjee, Nilanjan

AU - Loos, Ruth J F

AU - Boehnke, Michael

AU - McCarthy, Mark I.

AU - Ingelsson, Erik

AU - Lindgren, Cecilia M.

AU - Abecasis, Gonçalo R.

AU - Stefansson, Kari

AU - Frayling, Timothy M.

AU - Hirschhorn, Joel N.

AU - Morris, Andrew

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Research UK, United Kingdom

PY - 2010/10/14

Y1 - 2010/10/14

N2 - 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

AB - 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

U2 - 10.1038/nature09410

DO - 10.1038/nature09410

M3 - Article

C2 - 20881960

SN - 0028-0836

VL - 467

SP - 832

EP - 838

JO - Nature

JF - Nature

IS - 7317

ER -

Hundreds of variants clustered in genomic loci and biological pathways affect human height

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