Abstract

Abstract Background: The contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types. Methods: We estimated the proportion of phenotypic variation due to dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, non-melanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls. Results: We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. In contrast, additive effects ranged between 0.11 and 0.34. Conclusions: In line with studies of other human traits, dominance effects of common genetic variants play a minimal role in cancer etiology. Impact: These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.