Analysis of genetic dominance in the UK Biobank

• 成果类型: Article
• 署名作者: Palmer, Duncan S.; Zhou, Wei; Abbott, Liam; Wigdor, Emilie M.; Baya, Nikolas; Churchhouse, Claire; Seed, Cotton; Poterba, Tim; King, Daniel; Kanai, Masahiro; Bloemendal, Alex; Neale, Benjamin M.
• 署名单位: Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Wellcome Trust Sanger Institute; University of Oxford
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11912
• DOI: 10.1126/science.abn8455
• 发表日期: 2023-03-31
• 页码: 1341-+
• 关键词: ribavirin-induced anemia; human complex traits; missing heritability; mutations; itpa; epistasis; variance; polymorphism; association; expression

摘要

Classical statistical genetics theory defines dominance as any deviation from a purely additive, or dosage, effect of a genotype on a trait, which is known as the dominance deviation. Dominance is well documented in plant and animal breeding. Outside of rare monogenic traits, however, evidence in humans is limited. We systematically examined common genetic variation across 1060 traits in a large population cohort (UK Biobank, N = 361,194 samples analyzed) for evidence of dominance effects. We then developed a computationally efficient method to rapidly assess the aggregate contribution of dominance deviations to heritability. Lastly, observing that dominance associations are inherently less correlated between sites at a genomic locus than their additive counterparts, we explored whether they may be leveraged to identify causal variants more confidently.