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Genetic studies of body mass index yield new insights for obesity biology

Locke, Adam E
Kahali, Bratati
Berndt, Sonja I
Justice, Anne E
Pers, Tune H
Published in Nature. 2015, vol. 518, no. 7538, p. 197-206
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 Adipogenesis/geneticsAdiposity/geneticsAge FactorsBody Mass IndexContinental Population Groups/geneticsEnergy Metabolism/geneticsEurope/ethnologyFemaleGenetic Predisposition to Disease/geneticsGenome-Wide Association StudyGlutamic Acid/metabolismHumansInsulin/metabolism/secretionMaleObesity/genetics/metabolismPolymorphism, Single Nucleotide/geneticsQuantitative Trait Loci/geneticsSynapses/metabolism
PMID: 25673413
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Research group Traits génétiques complexes (901)
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LOCKE, Adam E et al. Genetic studies of body mass index yield new insights for obesity biology. In: Nature, 2015, vol. 518, n° 7538, p. 197-206. doi: 10.1038/nature14177 https://archive-ouverte.unige.ch/unige:90584

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Deposited on : 2016-12-20

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