Abstract
BACKGROUND: 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 caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma 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. By contrast, additive effects ranged between 0.11 and 0.34. CONCLUSIONS: In line with studies of other human traits, the 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.