MC1R and melanoma: Twelve of these loci exhibited no evidence of association to nevus count, but were strongly associated with melanoma risk, one of the most extreme being MC1R. A total of 18 loci showed pleiotropic action with consistent directional and proportional effects of all SNPs on nevi and melanoma risk, the strongest being MTAP, PLA2G6, and an intergenic region on 9q31.1 (Fig. 4a shows a bivariate regional association around GPRC5A, all loci are shown in Supplementary Figs 5–19).