Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability
Austin Hammermeister Suger1, Tabitha A Harrison1, Barbara Henning2
1Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
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.
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