MC1R and melanoma: These variants, such as the R alleles of MC1R, are known to be able to influence the risk of melanoma development even in individuals with established high‐penetrance melanoma predisposition alleles such as pathogenic variants in CDKN2A. Identifying a suitable control population of a sufficient size, that is well‐matched to carriers and has the same melanoma polygenic risk profile, poses an additional problem and can confound the analysis.