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. 2024 Oct 2;33(10):1383-1388.
doi: 10.1158/1055-9965.EPI-24-0496.

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

Austin Hammermeister Suger  1 , Tabitha A Harrison  1 , Barbara Henning  2 , Constance Turman  3 , Peter Kraft  3   4 , Sara Lindström  1   5
Affiliations

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

Austin Hammermeister Suger et al. Cancer Epidemiol Biomarkers Prev. .

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.

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Conflict of interest statement

Author Disclosures

The authors declare no potential conflicts of interest.

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