To explore enrichment for allelic heterogeneity in the tails and clinical classes of obesity, we performed conditional analyses using a method recently described by Yang et al.46 In these analyses, we found secondary signals that reached genome-wide significance (P<5×10-8) at 17 loci, including one locus for tails of BMI (FTO), 13 loci for tails of height (PTCH1 [two signals], GHSR, EDEM2, C6orf106, CRADD, EFEMP1, HHIP, FBXW11, NPR3, C2orf52, BCKDHB, EFR3B), one for tails of WHR (RSPO3), two for overweight (MC4R, FANCL), and one for obesity class I (FANCL; Supplementary Table 15). Whereas the secondary signals for tails of BMI (FTO) and WHR (RSPO3), and overweight and obesity class I (FANCL) have not been established previously, all 13 height loci identified here, as well as the MC4R locus have previously been shown to have allelic heterogeneity in the general population,7,9 suggesting that there is no enrichment in the tails for secondary signals (Supplementary Fig. 12-14).
