Genetic studies of body mass index yield new insights for obesity biology.
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Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
AuthorsLocke, AE; Kahali, B; Berndt, SI; Justice, AE; Pers, TH; Day, FR; Powell, C; Vedantam, S; Buchkovich, ML; Yang, J; Croteau-Chonka, DC; Esko, T; Fall, T; Ferreira, T; Gustafsson, S; Kutalik, Z; Luan, J; Mägi, R; Randall, JC; Winkler, TW; Wood, AR; Workalemahu, T; Faul, JD; Smith, JA; Hua Zhao, J; Zhao, W; Chen, J; Fehrmann, R; Hedman, ÅK; Karjalainen, J; Schmidt, EM; Absher, D; Amin, N; Anderson, D; Beekman, M; Bolton, JL; Bragg-Gresham, JL; Buyske, S; Demirkan, A; Deng, G; Ehret, GB; Feenstra, B; Feitosa, MF; Fischer, K; Goel, A; Gong, J; Jackson, AU; Kanoni, S; Kleber, ME; Kristiansson, K; Lim, U; Lotay, V; Mangino, M; Mateo Leach, I; Medina-Gomez, C; Medland, SE; Nalls, MA; Palmer, CD; Pasko, D; Pechlivanis, S; Peters, MJ; Prokopenko, I; Shungin, D; Stančáková, A; Strawbridge, RJ; Ju Sung, Y; Tanaka, T; Teumer, A; Trompet, S; van der Laan, SW; van Setten, J; Van Vliet-Ostaptchouk, JV; Wang, Z; Yengo, L; Zhang, W; Isaacs, A; Albrecht, E; Ärnlöv, J; Arscott, GM; Attwood, AP; Bandinelli, S; Barrett, A; Bas, IN; Bellis, C; Bennett, AJ; Berne, C; Blagieva, R; Blüher, M; Böhringer, S; Bonnycastle, LL; Böttcher, Y; Boyd, HA; Bruinenberg, M; Caspersen, IH; Ida Chen, Y-D; Clarke, R; Daw, EW; de Craen, AJM; Delgado, G; Dimitriou, M; et al.
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