Another point of distinction between our findings and those for BMI relates to the evidence for sexual dimorphism that we observed at several of the WHR-associated loci. Sex differences in the regulation of body fat distribution have long been acknowledged without a clear understanding of the underlying molecular mechanisms. These differences become apparent during puberty and are generally attributed to the influence of sex hormones33. Consistent with our findings, variance decomposition studies have shown that the genetic contribution to the overall variance in WHR, waist or hip circumference is greater in women17. While there is some evidence for loci with differential sex effects influencing lipids34, uric acid levels35 and risk of schizophrenia36, we are unaware of prior reports indicating such strong enrichment of female-specific associations for any other phenotype, including BMI32.
