Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Sonja I. Berndt, Stefan Gustafsson, Reedik Mägi, Andrea Ganna, Eleanor Wheeler, Mary F. Feitosa, Anne E. Justice, Keri L. Monda, Damien C. Croteau-Chonka, Felix R. Day, Tõnu Esko, Tove Fall, Teresa Ferreira, Davide Gentilini, Anne U. Jackson, Jianan Luan, Joshua C. Randall, Sailaja Vedantam, Cristen J. Willer, Thomas W. WinklerAndrew R. Wood, Tsegaselassie Workalemahu, Yi Juan Hu, Sang Hong Lee, Liming Liang, Dan Yu Lin, Josine L. Min, Benjamin M. Neale, Gudmar Thorleifsson, Jian Yang, Eva Albrecht, Najaf Amin, Jennifer L. Bragg-Gresham, Gemma Cadby, Martin Den Heijer, Niina Eklund, Krista Fischer, Anuj Goel, Jouke Jan Hottenga, Jennifer E. Huffman, Ivonne Jarick, Åsa Johansson, Toby Johnson, Stavroula Kanoni, Marcus E. Kleber, Inke R. König, Kati Kristiansson, Zoltán Kutalik, Claudia Lamina, Cecile Lecoeur, Guo Li, Massimo Mangino, Wendy L. McArdle, Carolina Medina-Gomez, Martina Müller-Nurasyid, Julius S. Ngwa, Ilja M. Nolte, Lavinia Paternoster, Sonali Pechlivanis, Markus Perola, Marjolein J. Peters, Michael Preuss, Lynda M. Rose, Jianxin Shi, Dmitry Shungin, Albert Vernon Smith, Rona J. Strawbridge, Ida Surakka, Alexander Teumer, Mieke D. Trip, Jonathan Tyrer, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Lindsay L. Waite, Jing Hua Zhao, Devin Absher, Folkert W. Asselbergs, Mustafa Atalay, Antony P. Attwood, Anthony J. Balmforth, Hanneke Basart, John Beilby, Lori L. Bonnycastle, Paolo Brambilla, Marcel Bruinenberg, Harry Campbell, Daniel I. Chasman, Peter S. Chines, Francis S. Collins, John M. Connell, William O Cookson, Ulf De Faire, Femmie De Vegt, Mariano Dei, Maria Dimitriou, Sarah Edkins, Karol Estrada, David M. Evans, Martin Farrall, Marco M. Ferrario, Jean Ferrières, Lude Franke, Francesca Frau, Pablo V. Gejman, Harald Grallert, Henrik Grönberg, Vilmundur Gudnason, Alistair S. Hall, Per Hall, Anna Liisa Hartikainen, Caroline Hayward, Nancy L. Heard-Costa, Andrew C. Heath, Johannes Hebebrand, Georg Homuth, Frank B. Hu, Sarah E. Hunt, Elina Hyppönen, Carlos Iribarren, Kevin B. Jacobs, John Olov Jansson, Antti Jula, Mika Kähönen, Sekar Kathiresan, Frank Kee, Kay Tee Khaw, Mika Kivimäki, Wolfgang Koenig, Aldi T. Kraja, Meena Kumari, Kari Kuulasmaa, Johanna Kuusisto, Jaana H. Laitinen, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Lars Lind, Jaana Lindström, Jianjun Liu, Antonio Liuzzi, Marja Liisa Lokki, Mattias Lorentzon, Pamela A. Madden, Patrik K. Magnusson, Paolo Manunta, Diana Marek, Winfried März, Irene Mateo Leach, Barbara McKnight, Sarah E. Medland, Evelin Mihailov, Lili Milani, Grant W. Montgomery, Vincent Mooser, Thomas W. Mühleisen, Patricia B. Munroe, Arthur W. Musk, Narisu Narisu, Gerjan Navis, George Nicholson, Ellen A. Nohr, Ken K. Ong, Ben A. Oostra, Colin N. Palmer, Aarno Palotie, John F. Peden, Nancy Pedersen, Annette Peters, Ozren Polasek, Anneli Pouta, Peter P. Pramstaller, Inga Prokopenko, Carolin Pütter, Aparna Radhakrishnan, Olli Raitakari, Augusto Rendon, Fernando Rivadeneira, Igor Rudan, Timo E. Saaristo, Jennifer G. Sambrook, Alan R. Sanders, Serena Sanna, Jouko Saramies, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, So Youn Shin, Stefano Signorini, Juha Sinisalo, Boris Skrobek, Nicole Soranzo, Alena Stancáková, Klaus Stark, Jonathan C. Stephens, Kathleen Stirrups, Ronald P. Stolk, Michael Stumvoll, Amy J. Swift, Eirini V. Theodoraki, Barbara Thorand, David Alexandre Tregouet, Elena Tremoli, Melanie M. Van Der Klauw, Joyce B. Van Meurs, Sita H. Vermeulen, Jorma Viikari, Jarmo Virtamo, Veronique Vitart, Gérard Waeber, Zhaoming Wang, Elisabeth Widén, Sarah H. Wild, Gonneke Willemsen, Bernhard R. Winkelmann, Jacqueline C. Witteman, Bruce H. Wolffenbuttel, Andrew Wong, Alan F. Wright, M. Carola Zillikens, Philippe Amouyel, Bernhard O. Boehm, Eric Boerwinkle, Dorret I. Boomsma, Mark J. Caulfield, Stephen J. Chanock, L. Adrienne Cupples, Daniele Cusi, George V. Dedoussis, Jeanette Erdmann, Johan G. Eriksson, Paul W. Franks, Philippe Froguel, Christian Gieger, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Christian Hengstenberg, Andrew A. Hicks, Aroon Hingorani, Anke Hinney, Albert Hofman, Kees G. Hovingh, Kristian Hveem, Thomas Illig, Marjo Riitta Jarvelin, Karl Heinz Jöckel, Sirkka M. Keinanen-Kiukaanniemi, Lambertus A. Kiemeney, Diana Kuh, Markku Laakso, Terho Lehtimäki, Douglas F. Levinson, Nicholas G. Martin, Andres Metspalu, Andrew D. Morris, Markku S. Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Willem H. Ouwehand, Lyle J. Palmer, Brenda Penninx, Chris Power, Michael A. Province, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Paul M. Ridker, Samuli Ripatti, Veikko Salomaa, Nilesh J. Samani, Harold Snieder, Thorkild I. Sørensen, Timothy D. Spector, Kari Stefansson, Anke Tönjes, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Pim Van Der Harst, Peter Vollenweider, Henri Wallaschofski, Nicholas J. Wareham, Hugh Watkins, H. Erich Wichmann, James F. Wilson, Goncalo R. Abecasis, Themistocles L. Assimes, Inês Barroso, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Timothy Frayling, Leif C. Groop, Talin Haritunian, Iris M. Heid, David Hunter, Robert C. Kaplan, Fredrik Karpe, Miriam F. Moffatt, Karen L. Mohlke, Jeffrey R. O'Connell, Yudi Pawitan, Eric E. Schadt, David Schlessinger, Valgerdur Steinthorsdottir, David P. Strachan, Unnur Thorsteinsdottir, Cornelia M. Van Duijn, Peter M. Visscher, Anna Maria Di Blasio, Joel N. Hirschhorn, Cecilia M. Lindgren, Andrew P. Morris, David Meyre, André Scherag, Mark I. McCarthy, Elizabeth K. Speliotes, Kari E. North, Ruth J. Loos, Erik Ingelsson

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Original languageEnglish (US)
Pages (from-to)501-512
Number of pages12
JournalNature Genetics
Volume45
Issue number5
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Genetics

Cite this

Berndt, S. I., Gustafsson, S., Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau-Chonka, D. C., Day, F. R., Esko, T., Fall, T., Ferreira, T., Gentilini, D., Jackson, A. U., Luan, J., Randall, J. C., Vedantam, S., Willer, C. J., ... Ingelsson, E. (2013). Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nature Genetics, 45(5), 501-512. https://doi.org/10.1038/ng.2606