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 | |
Publication status | Published - 11 Feb 2015 |
Research programs
- EMC COEUR-09
- EMC MGC-02-96-01
- EMC MM-01-39-04
- EMC MM-01-39-09-A
- EMC MM-01-52-07
- EMC NIHES-01-64-02
- EMC NIHES-04-55-01
- EMC OR-01-39-08