New genetic loci link adipose and insulin biology to body fat distribution

The LifeLines Cohort Study, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC, The ICBP, The International Endogene Consortium, The MAGIC Investigators, The MuTHER Consortium, The PAGE Consortium, The ReproGen Consortium

Research output: Contribution to journalArticle

483 Citations (Scopus)

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Original languageEnglish
Pages (from-to)187-196
Number of pages10
JournalNature
Volume518
Issue number7538
DOIs
Publication statusPublished - 12 Feb 2015
Externally publishedYes

Fingerprint

Body Fat Distribution
Genetic Loci
Waist-Hip Ratio
Waist Circumference
Hip
Body Mass Index
Insulin
Adipogenesis
Genome-Wide Association Study
Adiposity
Adipocytes
Sex Characteristics
Insulin Resistance
Meta-Analysis
Adipose Tissue
Fats
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

The LifeLines Cohort Study, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC, ... The ReproGen Consortium (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196. https://doi.org/10.1038/nature14132

New genetic loci link adipose and insulin biology to body fat distribution. / The LifeLines Cohort Study; The CARDIOGRAMplusC4D Consortium; The CKDGen Consortium; The GEFOS Consortium; The GENIE Consortium; The GLGC; The ICBP; The International Endogene Consortium; The MAGIC Investigators; The MuTHER Consortium; The PAGE Consortium; The ReproGen Consortium.

In: Nature, Vol. 518, No. 7538, 12.02.2015, p. 187-196.

Research output: Contribution to journalArticle

The LifeLines Cohort Study, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC, The ICBP, The International Endogene Consortium, The MAGIC Investigators, The MuTHER Consortium, The PAGE Consortium & The ReproGen Consortium 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, vol. 518, no. 7538, pp. 187-196. https://doi.org/10.1038/nature14132
The LifeLines Cohort Study, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015 Feb 12;518(7538):187-196. https://doi.org/10.1038/nature14132
The LifeLines Cohort Study ; The CARDIOGRAMplusC4D Consortium ; The CKDGen Consortium ; The GEFOS Consortium ; The GENIE Consortium ; The GLGC ; The ICBP ; The International Endogene Consortium ; The MAGIC Investigators ; The MuTHER Consortium ; The PAGE Consortium ; The ReproGen Consortium. / New genetic loci link adipose and insulin biology to body fat distribution. In: Nature. 2015 ; Vol. 518, No. 7538. pp. 187-196.
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