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

LifeLines Cohort Study, ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium

Research output: Contribution to journalArticlepeer-review

3276 Scopus citations

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 languageEnglish
Pages (from-to)197-206
Number of pages10
JournalNature
Volume518
Issue number7538
DOIs
StatePublished - 12 Feb 2015

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

Funding

FundersFunder number
National Institutes of HealthR01HL109946, P30GM103341, U01AG049505, R01DK089256, R01DK075787, UM1CA182913, P30HL107251
National Institute on Minority Health and Health DisparitiesP20MD006899

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