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

Sonja I. Berndt, Stefan Gustafsson, Reedik Maegi, Andrea Ganna, Eleanor Wheeler, Mary F. Feitosa, Anne E. Justice, Keri L. Monda, Damien C. Croteau-Chonka, Felix R. Day, Tonu Esko, Tove Fall, Teresa Ferreira, Davide Gentilini, Anne U. Jackson, Jian'an 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, Asa Johansson, Toby Johnson, Stavroula Kanoni, Marcus E. Kleber, Inke R. Koenig, Kati Kristiansson, Zoltn Kutalik, Claudia Lamina, Cecile Lecoeur, Guo Li, Massimo Mangino, Wendy L. McArdle, Carolina Medina-Gomez, Martina Mueller-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 Ferrieres, Lude Franke, Francesca Frau, Pablo V. Gejman, Harald Grallert, Henrik Groenberg, 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 Hyppoenen, Carlos Iribarren, Kevin B. Jacobs, John-Olov Jansson, Antti Jula, Mika Kahonen, Sekar Kathiresan, Frank Kee, Kay-Tee Khaw, Mika Kivimaki, Wolfgang König, Aldi T. Kraja, Meena Kumari, Kari Kuulasmaa, Johanna Kuusisto, Jaana H. Laitinen, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Lars Lind, Jaana Lindstrom, Jianjun Liu, Antonio Liuzzi, Marja-Liisa Lokki, Mattias Lorentzon, Pamela A. Madden, Patrik K. Magnusson, Paolo Manunta, Diana Marek, Winfried Maerz, 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. A. Palmer, Aarno Palotie, John F. Peden, Nancy Pedersen, Annette Peters, Ozren Polasek, Anneli Pouta, Peter P. Pramstaller, Inga Prokopenko, Carolin Puetter, 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 Stancakova, 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. J. van Meurs, Sita H. Vermeulen, Jorma Viikari, Jarmo Virtamo, Veronique Vitart, Gerard Waeber, Zhaoming Wang, Elisabeth Widen, Sarah H. Wild, Gonneke Willemsen, Bernhard R. Winkelmann, Jacqueline C. M. Witteman, Bruce H. R. 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 Lehtimaki, Douglas F. Levinson, Nicholas G. Martin, Andres Metspalu, Andrew D. Morris, Markku S. Nieminen, Inger Njolstad, 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. A. Sorensen, Timothy D. Spector, Kari Stefansson, Anke Tonjes, Jaakko Tuomilehto, Andre 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, Ines 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, Andr Scherag, Mark I. McCarthy, Elizabeth K. Speliotes, Kari E. North, Ruth J. F. Loos, Erik Ingelsson

    Research output: Contribution to journalArticle

    337 Citations (Scopus)

    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
    Pages (from-to)501-512
    Number of pages12
    JournalNature Genetics
    Volume45
    Issue number5
    DOIs
    Publication statusPublished - May 2013

    Keywords

    • Obesity
    • Polymorphism, Single Nucleotide
    • Body Height
    • Humans
    • Quantitative Trait Loci
    • Body Mass Index
    • Genome-Wide Association Study
    • Anthropometry
    • Genotype
    • Phenotype
    • Waist-Hip Ratio
    • European Continental Ancestry Group
    • Case-Control Studies
    • Genetic Predisposition to Disease
    • Meta-Analysis as Topic

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  • Cite this

    Berndt, S. I., Gustafsson, S., Maegi, 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