Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

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Thomas Illig; Marjo-Riitta Jarvelin; Jaakko Kaprio; Fredrik Karpe; Kay-Tee Khaw; Lambertus A Kiemeney; Heiko Krude; Markku Laakso; Debbie A Lawlor; Andres Metspalu; Patricia B Munroe; Willem H Ouwehand; Oluf Pedersen; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Thomas Quertermous; Thomas Reinehr; Aila Rissanen; Igor Rudan; Nilesh J Samani; Peter EH Schwarz; Alan R Shuldiner; Timothy D Spector; Jaakko Tuomilehto; Manuela Uda; André Uitterlinden; Timo T Valle; Martin Wabitsch; Gérard Waeber; Nicholas J Wareham; Hugh Watkins; Procardis Consortium; James F Wilson; Alan F Wright; M Carola Zillikens; Nilanjan Chatterjee; Steven A McCarroll; Shaun Purcell; Eric E Schadt; Peter M Visscher; Themistocles L Assimes; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Karen L Mohlke; Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Cornelia M van Duijn; H-Erich Wichmann; Timothy M Frayling; Unnur Thorsteinsdottir; Gonçalo R Abecasis; Inês Barroso; Michael Boehnke; Kari Stefansson; Kari E North; Mark I McCarthy; Joel N Hirschhorn; Erik Ingelsson; Ruth JF Loos; (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature genetics, 42 (11). pp. 937-948. ISSN 1061-4036 DOI: 10.1038/ng.686
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Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.


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