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.
Original language | English |
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Pages (from-to) | 197-206 |
Number of pages | 10 |
Journal | Nature |
Volume | 518 |
Issue number | 7538 |
DOIs | |
State | Published - 12 Feb 2015 |
Bibliographical note
Publisher Copyright:© 2015 Macmillan Publishers Limited. All rights reserved.
Funding
Funders | Funder number |
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National Institutes of Health | R01HL109946, P30GM103341, U01AG049505, R01DK089256, R01DK075787, UM1CA182913, P30HL107251 |
National Institute on Minority Health and Health Disparities | P20MD006899 |