PLoS Genetics · 2009 · 34 citations · 41 references
Life SciencesGeneticsMolecular GeneticsGenetic EpidemiologyHuman GeneticsMedical GeneticsAdipose TissueDisease Susceptibility LociGenome-wide Association StudiesGenotype-phenotype Association AnalysisMarker-trait AssociationObesity EpidemiologyAbdominal AdiposityFat DistributionGenetic Susceptibility To ObesityIncreased AdiposityMeta-analysis Of Genetic Association StudiesObesity SusceptibilityWaist Circumference MeasurementWaist-to-hip Ratio
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 = 1.9610 211 ) and MSRA (WC, P = 8.9610 29 ). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6610 28 ). 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.
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