Genetic studies of body mass index yield new insights for obesity biology
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Publication date
2015-02-12
Authors
Locke, Adam E.
Kahali, Bratati
Berndt, Sonja I.
Justice, Anne E.
Pers, Tune H.
Day, Felix R.
Powell, Corey
Vedantam, Sailaja
Buchkovich, Martin L.
Yang, Jian
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Document Type
Article
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taverne
Abstract
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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 x 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 similar to 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 systemin 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.
Keywords
GENOME-WIDE ASSOCIATION, PROVIDES INSIGHTS, GLYCEMIC TRAITS, HUMAN HEIGHT, LOCI, METAANALYSIS, VARIANTS, EXPRESSION, PATHWAYS, ARCHITECTURE, Taverne
Citation
Locke, A E, Kahali, B, Berndt, S I, Justice, A E, Pers, T H, Day, F R, Powell, C, Vedantam, S, Buchkovich, M L, Yang, J, Croteau-Chonka, D C, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Maegi, R, Randall, J C, Winkler, T W, Wood, A R, Workalemahu, T, Faul, J D, Smith, J A, Zhao, J H, Zhao, W, Chen, J, Fehrmann, R, Hedman, A K, Karjalainen, J, Schmidt, E M, Absher, D, Amin, N, Anderson, D, van der Laan, S W, van Setten, J, Uh, H-W, den Ruijter, H M, Moll, F L, Pasterkamp, G, Asselbergs, F W, de Bakker, P I W, Zanen, P, LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Grp, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium & Int Endogene Consortium 2015, 'Genetic studies of body mass index yield new insights for obesity biology', Nature, vol. 518, no. 7538, pp. 197-206. https://doi.org/10.1038/nature14177