Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability

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.

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.

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.

In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology.

These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.