Editors' ChoiceGenetics

Fitting the Genes into Your Waist

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Science Translational Medicine  26 Jun 2013:
Vol. 5, Issue 191, pp. 191ec107
DOI: 10.1126/scitranslmed.3006774

Men tend to be taller, heavier, and leaner than women. To dissect the genetics underlying these sex differences, Randall and colleagues assessed over 270,000 people and found seven single-nucleotide polymorphisms that are significantly associated with waist features in women but show little to no evidence of association in men.

In this meta-analysis of studies conducted by the Genetic Investigation of ANthropometric Traits (GIANT) consortium, the authors tested for genetic associations separately for men and women, under a range of models. They examined an array of body-shape related phenotypes: height, weight, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. The authors identified seven genome-wide significant loci with sex-specific effects; six of these were found to be associated with waist-to-hip ratio (after correction for BMI), and the seventh was associated with waist circumference (also after correction for BMI). The effects of these loci were all found to be specific to women; these loci had almost no association with these phenotypes in men. In epidemiological studies, waist-to-hip ratio is strongly associated with the risk of death and is thought to reflect fat distribution because the effects of BMI are controlled for in the phenotype.

Among the seven loci, three were previously unidentified associations, one of which was PPARG. This finding is of particular importance because PPARG plays a prominent role in the genesis of type 2 diabetes and is a target for current therapies. Taken together, the results demonstrate that for some traits sexual dimorphism is a component of the variation in the population and that new sex-specific biology can be uncovered with such an approach. They also point to the wisdom of conducting sex-specific analyses in genetic association studies.

J. C. Randall et al., Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genet. 9, e1003500 (2013). [Full Text]

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