Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution

PLoS Genet. 2009 Jun;5(6):e1000508. doi: 10.1371/journal.pgen.1000508. Epub 2009 Jun 26.

Abstract

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Adult
  • Body Fat Distribution*
  • Cohort Studies
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Lysophospholipase / genetics*
  • Male
  • Methionine Sulfoxide Reductases
  • Obesity / genetics*
  • Obesity / metabolism
  • Oxidoreductases / genetics*
  • Polymorphism, Single Nucleotide
  • Transcription Factor AP-2 / genetics*
  • Waist Circumference
  • Waist-Hip Ratio

Substances

  • TFAP2B protein, human
  • Transcription Factor AP-2
  • Oxidoreductases
  • Methionine Sulfoxide Reductases
  • methionine sulfoxide reductase
  • Lysophospholipase

Grant support