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

IF 3.7 3区医学 Q2 ONCOLOGY Cancer Epidemiology Biomarkers & Prevention Pub Date : 2024-10-02 DOI:10.1158/1055-9965.EPI-24-0496

Austin Hammermeister Suger, Tabitha A Harrison, Barbara Henning, Constance Turman, Peter Kraft, Sara Lindström

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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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常见遗传变异的非加成效应对癌症遗传性的影响微乎其微。

背景：显性效应对癌症遗传性的贡献尚不清楚。我们利用现有的七种癌症的全基因组关联数据来估计优势效应对单个癌症类型遗传率的贡献：方法：我们利用七种癌症（乳腺癌、结直肠癌、肺癌、黑色素瘤、非黑色素瘤皮肤癌、卵巢癌和前列腺癌）的全基因组关联数据，对166772例病例和284824例对照的表型变异比例进行了估计：我们没有发现任何证据表明显性效应对癌症遗传性有重大影响。相反，加性效应介于 0.11 和 0.34 之间：结论：与对人类其他性状的研究一致，常见遗传变异的显性效应在癌症病因学中的作用微乎其微：这些结果支持在进行常见遗传变异的癌症关联研究时采用加性遗传模型的假设。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Epidemiology Biomarkers & Prevention 医学-公共卫生、环境卫生与职业卫生

CiteScore

6.50

自引率

2.60%

发文量

538

审稿时长

1.6 months

期刊介绍： Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.