To determine whether the WHR-associated signals exert their effects primarily through an effect on waist (WC) or hip circumference (HIP), we performed meta-analyses for these specific phenotypes in the discovery and follow-up studies (Supplementary Table 1 and 3). Overall, we observed stronger associations for HIP than for WC. Effect-size estimates were numerically greater for HIP than for WC at eleven of the 14 loci, and there were nominal associations (P < 0.05) with HIP for twelve of the WHR-associated loci but only four associations with WC. In both sexes, the WHR-associated loci displaying nominal association with HIP always featured the WHR-increasing allele associated with reduced HIP. In contrast, we observed sexual dimorphism in the pattern of WC associations. In women, the WHR-increasing allele at all 14 loci was associated with increased WC, whereas this was only true for 6 of these loci in men (Figure 3). At GRB14, for example, the WHR-increasing allele was associated with increased WC in women (P = 3.6 × 10−4) but decreased WC in men (P = 6.8 × 10−3). These differences in the relationships between WC, HIP and WHR underlie some of the sexual dimorphism in the patterns of WHR association.
