Analysis of genetic dominance in the UK Biobank
Analysis of genetic dominance in the UK Biobank
Classical statistical genetic theory defines dominance as a deviation from a purely additive effect. Dominance is well documented in model organisms and plant/animal breeding; outside of rare monogenic traits, however, evidence in humans is limited. We evaluated dominance effects in >1,000 phenotypes in the UK Biobank through GWAS, identifying 175 genome-wide significant loci (P < 4.7 × 10?11). Power to detect non-additive loci is low: we estimate a 20-30 fold increase in sample size is required to detect dominance loci to significance levels observed at additive loci. By deriving a new dominance form of LD-score regression, we found no evidence of a dominance contribution to phenotypic variance tagged by common variation genome-wide (median fraction 5.73 × 10?4). We introduce dominance fine-mapping to explore whether the more rapid decay of dominance linkage disequilibrium can be leveraged to find causal variants. These results provide the most comprehensive assessment of dominance trait variation in humans to date.
Zhou Wei、Bloemendal Alex、Palmer Duncan S.、Seed Cotton、Churchhouse Claire、Neale Benjamin M.、Baya Nikolas、Abbott Liam、King Daniel、Poterba Tim、Kanai Masahiro
Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and HarvardStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and HarvardAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
遗传学生物科学研究方法、生物科学研究技术基础医学
Zhou Wei,Bloemendal Alex,Palmer Duncan S.,Seed Cotton,Churchhouse Claire,Neale Benjamin M.,Baya Nikolas,Abbott Liam,King Daniel,Poterba Tim,Kanai Masahiro.Analysis of genetic dominance in the UK Biobank[EB/OL].(2025-03-28)[2025-06-13].https://www.biorxiv.org/content/10.1101/2021.08.15.456387.点此复制
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