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, Andrew P. Morris, 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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)832-838
Number of pages7
JournalNature
Volume467
Issue number7317
DOIs
Publication statusPublished - Oct 14 2010

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    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., ... Hirschhorn, J. N. (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