There are several potential explanations that could potentially account for our observed genetic association, particularly the marked sexual dimorphism. It has been previously shown that the familial contribution to fat distribution phenotypes is stronger in women as compared to men [33]. This concept is further strengthened by findings in mice suggesting that gonadal hormones are important in the sex-specific expression of genes related to metabolic traits [51]. In addition, known gender differences in fat distribution may also in part contribute to our findings, as women have been shown to have more subcutaneous fat but less visceral fat compared to men [20]. The relatively smaller amount of visceral fat in women may have increased our ability to detect a genetic signal. Finally, we have consistently observed stronger associations among women as compared to men with respect to metabolic risk factors in association with VAT [20]. While the reasons for this have not been fully elucidated, the stronger associations in women as compared to men is similar to what we have observed in the present analysis and in a prior GWAS of fat distribution phenotypes [32].
