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

Summary, in English

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-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 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 x 10(-3) to P = 1.2 x 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.

• Författare: Iris M. Heid; Anne U. Jackson; Joshua C. Randall; Thomas W. Winkler; Lu Qi; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; M. Carola Zillikens; Elizabeth K. Speliotes; Reedik Maegi; Tsegaselassie Workalemahu; Charles C. White; Nabila Bouatia-Naji; Tamara B. Harris; Sonja I. Berndt; Erik Ingelsson; Cristen J. Willer; Michael N. Weedon; Jianan Luan; Sailaja Vedantam; Tonu Esko; Tuomas O. Kilpelaeinen; Zoltan Kutalik; Shengxu Li; Keri L. Monda; Anna L. Dixon; Christopher C. Holmes; Lee M. Kaplan; Liming Liang; Josine L. Min; Miriam F. Moffatt; Cliona Molony; George Nicholson; Eric E. Schadt; Krina T. Zondervan; Mary F. Feitosa; Teresa Ferreira; Hana Lango Allen; Robert J. Weyant; Eleanor Wheeler; Andrew R. Wood; Karol Estrada; Michael E. Goddard; Guillaume Lettre; Massimo Mangino; Dale R. Nyholt; Shaun Purcell; Albert Vernon Smith; Peter M. Visscher; Jian Yang; Steven A. McCarroll; James Nemesh; Benjamin F. Voight; Devin Absher; Najaf Amin; Thor Aspelund; Lachlan Coin; Nicole L. Glazer; Caroline Hayward; Nancy L. Heard-Costa; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Marika Kaakinen; Karen Kapur; Shamika Ketkar; Joshua W. Knowles; Peter Kraft; Aldi T. Kraja; Claudia Lamina; Michael F. Leitzmann; Barbara McKnight; Andrew P. Morris; Ken K. Ong; John R. B. Perry; Marjolein J. Peters; Ozren Polasek; Inga Prokopenko; Nigel W. Rayner; Samuli Ripatti; Fernando Rivadeneira; Neil R. Robertson; Serena Sanna; Ulla Sovio; Ida Surakka; Alexander Teumer; Sophie van Wingerden; Veronique Vitart; Jing Hua Zhao; Christine Cavalcanti-Proenca; Peter S. Chines; Eva Fisher; Jennifer R. Kulzer; Cecile Lecoeur; Narisu Narisu; Camilla Sandholt; Laura J. Scott; Kaisa Silander; Klaus Stark; Mari-Liis Tammesoo; Tanya M. Teslovich; Nicholas John Timpson; Richard M. Watanabe; Ryan Welch; Daniel I. Chasman; Matthew N. Cooper; John-Olov Jansson; Johannes Kettunen; Robert W. Lawrence; 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 N. M. Day; Mariano Dei; Marcus Doerr; Paul Elliott; Michael R. Erdos; Johan G. Eriksson; Nelson B. Freimer; Mao Fu; Stefan Gaget; Eco J. C. Geus; Anette P. Gjesing; Harald Grallert; Juergen Graessler; Christopher J. Groves; Candace Guiducci; Anna-Liisa Hartikainen; Neelam Hassanali; Aki S. Havulinna; Karl-Heinz Herzig; Andrew A. Hicks; Jennie Hui; Wilmar Igl; Pekka Jousilahti; Antti Jula; Eero Kajantie; Leena Kinnunen; Ivana Kolcic; Seppo Koskinen; Peter Kovacs; Heyo K. Kroemer; Vjekoslav Krzelj; Johanna Kuusisto; Kirsti Kvaloy; Jaana Laitinen; Olivier Lantieri; G. Mark Lathrop; Marja-Liisa Lokki; Robert N. Luben; Barbara Ludwig; Wendy L. McArdle; Anne McCarthy; Mario A. Morken; Mari Nelis; Matt J. Neville; Guillaume Pare; Alex N. Parker; John F. Peden; Irene Pichler; Kirsi H. Pietilainen; Carl G. P. Platou; Anneli Pouta; Martin Ridderstråle; Nilesh J. Samani; Jouko Saramies; Juha Sinisalo; Jan H. Smit; Rona J. Strawbridge; Heather M. Stringham; Amy J. Swift; Maris Teder-Laving; Brian Thomson; Gianluca Usala; Joyce B. J. van Meurs; Gert-Jan van Ommen; Vincent Vatin; Claudia B. Volpato; Henri Wallaschofski; G. Bragi Walters; Elisabeth Widen; Sarah H. Wild; Gonneke Willemsen; Daniel R. Witte; Lina Zgaga; Paavo Zitting; John P. Beilby; Alan L. James; Mika Kahonen; Terho Lehtimaki; Markku S. Nieminen; Claes Ohlsson; Lyle J. Palmer; Olli Raitakari; Paul M. Ridker; Michael Stumvoll; Anke Toenjes; Jorma Viikari; Beverley Balkau; Yoav Ben-Shlomo; Richard N. Bergman; Heiner Boeing; George Davey Smith; Shah Ebrahim; Philippe Froguel; Torben Hansen; Christian Hengstenberg; Kristian Hveem; Bo Isomaa; Torben Jorgensen; Fredrik Karpe; Kay-Tee Khaw; Markku Laakso; Debbie A. Lawlor; Michel Marre; Thomas Meitinger; Andres Metspalu; Kristian Midthjell; Oluf Pedersen; Veikko Salomaa; Peter E. H. Schwarz; Tiinamaija Tuomi; Jaakko Tuomilehto; Timo T. Valle; Nicholas J. Wareham; Alice M. Arnold; Jacques S. Beckmann; Sven Bergmann; Eric Boerwinkle; Dorret I. Boomsma; Mark J. Caulfield; Francis S. Collins; Gudny Eiriksdottir; Vilmundur Gudnason; Ulf Gyllensten; Anders Hamsten; Andrew T. 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 W. Penninx; Peter P. Pramstaller; Bruce M. Psaty; Thomas Quertermous; Aila Rissanen; Igor Rudan; Alan R. Shuldiner; Nicole Soranzo; Timothy D. Spector; Ann-Christine Syvanen; Manuela Uda; Andre Uitterlinden; Henry Voelzke; Peter Vollenweider; James F. Wilson; Jacqueline C. Witteman; Alan F. Wright; Goncalo R. Abecasis; Michael Boehnke; Ingrid B. Borecki; Panos Deloukas; Timothy M. Frayling; Leif Groop; Talin Haritunians; David J. Hunter; Robert C. Kaplan; Kari E. North; Jeffrey R. O'Connell; Leena Peltonen; David Schlessinger; David P. Strachan; Joel N. Hirschhorn; Themistocles L. Assimes; H-Erich Wichmann; Unnur Thorsteinsdottir; Cornelia M. van Duijn; Kari Stefansson; L. Adrienne Cupples; Ruth J. F. Loos; Ines Barroso; Mark I. McCarthy; Caroline S. Fox; Karen L. Mohlke; Cecilia M. Lindgren
• Avdelning/ar: Translationell Muskel Forskning; Diabetes - Clinical Obesity; EXODIAB: Excellence of Diabetes Research in Sweden
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 160-949
• Publikation/Tidskrift/Serie: Nature Genetics
• Volym: 42
• Issue: 11
• Länkar: http://dx.doi.org/10.1038/ng.685
• Dokumenttyp: Artikel i tidskrift
• Förlag: Nature Publishing Group
• Ämne: Nutrition and Dietetics; Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Translational Muscle Research; Diabetes - Clinical Obesity
• ISBN/ISSN/Övrigt: ISSN: 1546-1718