Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Iris M. Heid, Anne U. Jackson, Joshua C. Randall, Tthomas W. Winkler, Llu Qi, Valgerdur Ssteinthorsdottir, Ggudmar Tthorleifsson, Ccarola Zillikens, Eelizabeth K. Sspeliotes, Reedik Mägi, Tsegaselassie Workalemahu, Charles White, Nabila Bouatia-Naji, Tamara B. Harris, Ssonja I. Berndt, Eerik Ingelsson, Cristen J. Willer, Michael N. Weedon, Jian'An Luan, Ssailaja VedantamTõnu Eesko, Tuomas O. Kilpeläinen, Zoltán Kutalik, Sshengxu Li, Keri L. Monda, Anna Dixon, Christopher Holmes, Lee Kaplan, Liming Liang, Josine Min, Miriam F. Moffatt, Cliona Molony, Ggeorge Nicholson, Eeric E. Sschadt, Krina T. Zondervan, Mary F. Feitosa, Teresa Ferreira, Hana Lango Allen, Robert J. Weyant, Eeleanor Wheeler, Andrew R. Wood, Magic, Karol Eestrada, Micheal E. Goddard, Guillaume Lettre, Massimo Mangino, Dale R. Nyholt, Sshaun Purcell, Albert Vernon Ssmith, Peter Visscher, Jian Yang, Ssteven A. McCcarroll, James Nemesh, Benjamin F. Voight, Devin Absher, Najaf Amin, Thor Aspelund, Lachlan Coin, Nicole Glazer, Caroline Hayward, Nancy Heard-Ccosta, Jouke Jan Hottenga, Åsa Johansson, Toby Johnson, Marika Kaakinen, Karen Kapur, Sshamika Ketkar, Joshua Knowles, Peter Kraft, Aldi Kraja, Claudia Lamina, Micheal F. Leitzmann, Barbara McKknight, Andrew P. Morris, Ken Oong, John R.B. Perry, Marjolein J. Peters, Oozren Polasek, Inga Prokopenko, Nigel Rayner, Ssamuli Ripatti, Fernando Rivadeneira, Neil R. Robertson, Serena Sanna, Ulla Sovio, Ida Surakka, Alexander Teumer, Sophie Van Wingerden, Veronique Vitart, Jing Hua Zhao, Christine Cavalcanti-Proença, Peter S. Chines, Eeva Fisher, Jennifer R. Kulzer, Cecile Lecoeur, Narisu Narisu, Camilla Sandholt, Laura J. Scott, Kaisa Silander, Klaus Stark, Mari Lliis Tammesoo, Tanya M. Teslovich, Nicholas John Timpson, Richard Watanabe, Ryan Welch, Daniel I. Chasman, Matthew N. Cooper, John Oolov Jansson, Johannes Kettunen, Robert Wlawrence, Niina Pellikka, Markus Perola, Liesbeth Vandenput, Helene Alavere, Peter Almgren, Larry D. Atwood, Amanda J. Bennett, Reiner Biffar, Lori L. Bonnycastle, Stefan R. Bornstein, Thomas A. Buchanan, Harry Campbell, Ian Day, Mariano Dei, Marcus Dörr, Paul Eelliott, Michael R. Eerdos, Johan G. Eeriksson, Nelson B. Freimer, Mao Fu, Stefan Gaget, Eeco J.C. Geus, Anette P. Gjesing, Harald Grallert, Jürgen Gräßler, Christopher J. Groves, Candace Guiducci, Anna Lliisa Hartikainen, Neelam Hassanali, Aki S. Havulinna, Karl Heinz Herzig, Andrew A. Hicks, Jennie Hui, Wilmar Igl, Pekka Jousilahti, Antti Jula, Eeero Kajantie, Leena Kinnunen, Ivana Kolcic, Seppo Koskinen, Peter Kovacs, Heyo K. Kroemer, Vjekoslav Krzelj, Johanna Kuusisto, Kirsti Kvaloy, Jaana Laitinen, Oolivier Lantieri, Mark Lathrop, Marja Llokki Lokki, Robert Luben, Barbara Ludwig, Wendy McArdle, Anne McCcarthy, Mario A. Morken, Mari Nelis, Matt J. Neville, Guillaume Paré, Alex Parker, John F. Peden, Irene Pichler, Kirsi H. Pietiläinen, Carl P. Platou, Anneli Pouta, Martin Ridderstråle, Nilesh J. Samani, Jouko Saramies, Juha Sinisalo, Jan H. Smit, Rona J. Strawbridge, Heather Stringham, Amy J. Swift, Maris Teder-Llaving, Brian Thomson, Gianluca Usala, Joyce B.J. Van Mmeurs, Gert Jan Van Ommen, Vincent Vatin, Claudia B. Volpato, Henri Wallaschofski, Bragi Walters, Eelisabeth Widen, Sarah H. Wild, Gonneke Willemsen, Deniel R. Witte, Lina Zgaga, Paavo Zitting, John P. Beilby, Alan James, Mika Kähönen, Terho Lehtimäki, Markku Nieminen, Claes Ohlsson, Lyle J. Palmer, Olli Raitakari, Paul Ridker, Micheal Stumvoll, Anke Tönjes, Jorma Viikari, Beverley Balkau, Yoav Ben-Shlomo, Richard Bergman, Heiner Boeing, George Ddavey Smith, Shah Eebrahim, Philippe Froguel, Torben Hansen, Christian Hengstenberg, Kristian Hveem, Bo Isomaa, Torben Jørgensen, Fredrik Karpe, Kay Ttee Khaw, Markku Laakso, Debbie A. Lawlor, Michel Marre, Thomas Meitinger, Andres Metspalu, Kristian Midthjell, Oluf Pedersen, Veikko Salomaa, Peter Ee H. Schwarz, Tiinamaija Tuomi, Jaakko Tuomilehto, Timo T. Valle, Nicholas J. Wareham, Alice Arnold, Jacques Beckmann, Sven Bergmann, Eeric Boerwinkle, Dorret I. Boomsma, Mark J. Caulfield, Francis Collins, Gudny Eeiriksdottir, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Andrew Hattersley, Albert Hofman, Frank B. Hu, Thomas Illig, Carlos Iribarren, Marjo Riitta Jarvelin, W. H.Linda Kao, Jaakko Kaprio, Lenore J. Launer, Patricia B. Munroe, Ben Oostra, Brenda Penninx, Peter P. Pramstaller, Bruce Psaty, Thomas Quertermous, Aila Rissanen, Igor Rudan, Alan R. Shuldiner, Nicole Soranzo, Timothy Spector, Ann Cchristine Syvanen, Manuela Uda, André Uitterlinden, Henry Völzke, Peter Vollenweider, James F. Wilson, Jacqueline Witteman, Alan F. Wright, Gonçalo R. Abecasis, Micheal Boehnke, Ingrid B. Borecki, Panos Deloukas, Timothy M. Frayling, Leif Groop, Talin Haritunians, David J. Hunter, Robert Kaplan, Kari North, Jeffrey R. O'Cconnell, Leena Peltonen, David Schlessinger, David P. Strachan, Joel Hirschhorn, Themistocles Assimes, H. Eerich Wichmann, Unnur Thorsteinsdottir, Cornelia Van Dduijn, Kari Stefansson, Adrienne Cupples, Ruth J.F. Loos, Inês Barroso, Mark I. McCcarthy, Caroline Fox, Karen Mohlke, Cecilia Lindgren

Research output: Contribution to journalArticle

634 Scopus citations

Abstract

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Original languageEnglish (US)
Pages (from-to)949-960
Number of pages12
JournalNature Genetics
Volume42
Issue number11
DOIs
StatePublished - Nov 1 2010

ASJC Scopus subject areas

  • Genetics

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    Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Ssteinthorsdottir, V., Tthorleifsson, G., Zillikens, C., Sspeliotes, E. K., Mägi, R., Workalemahu, T., White, C., Bouatia-Naji, N., Harris, T. B., Berndt, S. I., Ingelsson, E., Willer, C. J., Weedon, M. N., Luan, JA., ... Lindgren, C. (2010). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genetics, 42(11), 949-960. https://doi.org/10.1038/ng.685