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Genetic studies of body mass index yield new insights for obesity biology
Locke, A Bratati, K Berndt, S Justice, A Pers, T Day, F Powell, C Vedantam Buchkovich, M Vandenput, Liesbeth
Locke, A
Bratati, K
Berndt, S
Justice, A
Pers, T
Day, F
Powell, C
Vedantam
Buchkovich, M
Vandenput, Liesbeth
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.
Keywords
association study, genome-wide, meta analysis, obesity, body mass index, BMI
Date
2015
Type
Journal article
Journal
Book
Volume
518
Issue
7538
Page Range
197-206
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
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© 2015 Macmillan Publishers Limited. All rights reserved