By providing novel insights into the regulation of body fat distribution, the present study raises a number of issues for future investigation. From the genetic perspective, re-sequencing, dense-array genotyping and fine-mapping approaches will be required to characterize causal variants at the loci we have identified, and to support further discoveries that may account for the substantial proportion of genetic variance unexplained by our findings. From the clinical perspective, it will be important to explore the relationship of these variants to more refined measures of body fat distribution derived from detailed imaging studies, to use the variants identified to characterise the causal relationships between body fat distribution and related metabolic and cardiovascular traits, and to explore ethnic differences in patterns of body fat distribution. Efforts to tackle overall obesity through therapeutic or lifestyle-based modulation of overall energy balance have proved extremely challenging to implement, and the manipulation of processes associated with more beneficial patterns of fat distribution offers an alternative perspective for future drug discovery.
