Document Type
Article
Publication Date
2-12-2015
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 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.
Publication Source (Journal or Book title)
Nature
First Page
197
Last Page
206
Recommended Citation
Locke, A., Kahali, B., Berndt, S., Justice, A., Pers, T., Day, F., Powell, C., Vedantam, S., Buchkovich, M., Yang, J., Croteau-Chonka, D., Esko, T., Fall, T., Ferreira, T., Gustafsson, S., Kutalik, Z., Luan, J., Mägi, R., Randall, J., Winkler, T., Wood, A., Workalemahu, T., Faul, J., Smith, J., Zhao, J., Zhao, W., Chen, J., Fehrmann, R., Hedman, K., Karjalainen, J., Schmidt, E., Absher, D., & Amin, N. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518 (7538), 197-206. https://doi.org/10.1038/nature14177