The primary objective of genetic discovery efforts is to characterize the specific mechanisms involved in the regulation of the trait of interest. Despite the considerable challenges associated with moving from common variant association signals to definition of the causal alleles and pathways, we have identified strong candidates at several of the loci. For example, the cis-eQTL data implicate GRB14 as a compelling candidate for the WHR-association on chromosome 2, and we were able to show that the same GRB14 variants are also associated with triglyceride and insulin levels, consistent with previous association of this locus with HDL-cholesterol 37. These inferences about the role of GRB14 are supported by evidence that Grb14-deficient mice exhibit improved glucose homeostasis despite lower circulating insulin levels, and enhanced insulin signaling in liver and skeletal muscle38. The signal near ADAMTS9 overlaps a previously-reported T2D locus39, and the lead SNP for WHR in our study is identical to the SNP displaying the strongest T2D association in an expanded T2D meta-analysis40. Given evidence that ADAMTS9 T2D-risk alleles are associated with insulin resistance in peripheral tissues41, these findings are
