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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.

Original publication

DOI

10.1371/journal.pgen.1000508

Type

Journal article

Journal

PLoS Genet

Publication Date

06/2009

Volume

5

Keywords

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