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

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

Research output: Contribution to journalArticle

1335 Citations (Scopus)

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
Publication statusPublished - 12 Feb 2015
Externally publishedYes

Fingerprint

Body Mass Index
Obesity
Adipogenesis
Genome-Wide Association Study
Adiposity
Energy Metabolism
Meta-Analysis
Glutamic Acid
Central Nervous System
Insulin
Lipids
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, ... The International Endogene Consortium (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206. https://doi.org/10.1038/nature14177

Genetic studies of body mass index yield new insights for obesity biology. / The LifeLines Cohort Study; The ADIPOGen Consortium; The AGEN-BMI Working Group; The CARDIOGRAMplusC4D Consortium; The CKDGen Consortium; The GLGC; The ICBP; The MAGIC Investigators; The MuTHER Consortium; The MIGen Consortium; The PAGE Consortium; The ReproGen Consortium; The GENIE Consortium; The International Endogene Consortium.

In: Nature, Vol. 518, No. 7538, 12.02.2015, p. 197-206.

Research output: Contribution to journalArticle

The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium & The International Endogene Consortium 2015, 'Genetic studies of body mass index yield new insights for obesity biology', Nature, vol. 518, no. 7538, pp. 197-206. https://doi.org/10.1038/nature14177
The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015 Feb 12;518(7538):197-206. https://doi.org/10.1038/nature14177
The LifeLines Cohort Study ; The ADIPOGen Consortium ; The AGEN-BMI Working Group ; The CARDIOGRAMplusC4D Consortium ; The CKDGen Consortium ; The GLGC ; The ICBP ; The MAGIC Investigators ; The MuTHER Consortium ; The MIGen Consortium ; The PAGE Consortium ; The ReproGen Consortium ; The GENIE Consortium ; The International Endogene Consortium. / Genetic studies of body mass index yield new insights for obesity biology. In: Nature. 2015 ; Vol. 518, No. 7538. pp. 197-206.
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