To investigate differences in genetic architecture between the tails and full distributions, we estimated whether the observed genetic effects in tails of BMI, height and WHR were different from what would be expected based on the full distributions of corresponding traits. To do this, we first estimated the expected effect for each SNP in the tails based on the full distribution in each study and then meta-analyzed the expected associations across studies. The Q-Q plots of P-values testing differences between the observed and expected (Fig. 1 and Supplementary Fig. 9) did not show any enrichment, indicating that effect sizes observed in tails and those expected based on the overall distribution were similar. Further, comparable results were observed for the 32 SNPs previously associated with BMI in Speliotes et al4, as well as for previously published and novel extreme obesity loci (Supplementary Table 12).
