Findings and insights from the genetic investigation of age of first reported occurrence for complex disorders in the UK Biobank and FinnGen
Findings and insights from the genetic investigation of age of first reported occurrence for complex disorders in the UK Biobank and FinnGen
Abstract Age of onset contains information on the timing of events relevant to disease etiology, but there has not been a systematic investigation of its heritability from GWAS data. Here, we characterize the genetic architecture of age of first occurrence and its genomic relationship with disease susceptibility for a wide range of complex disorders in the UK Biobank. For diseases with a sufficient sample size, we discover that age of first occurrence has non-trivial genetic contributions, some with specific genetic risk factors not associated with susceptibility to the disease. Through genetic correlation analysis, we show that an earlier health-event occurrence is correlated with a higher polygenic risk of disease susceptibility. An independent genetic investigation of the FinnGen cohort replicates the pattern of heritability and genetic correlation estimates. We then demonstrate that incorporating disease onset age with susceptibility may improve genetic risk prediction and stratification.
Cordioli Mattia、Smoller Jordan W.、Feng Yen-Chen A.、FinnGen、Neale Benjamin M.、Ganna Andrea、Ge Tian
Institute for Molecular Medicine Finland, University of HelsinkiPsychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Harvard Medical SchoolPsychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital||Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and HarvardAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Harvard Medical School||Program in Medical and Population Genetics, Broad Institute of Harvard and MITAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital||Program in Medical and Population Genetics, Broad Institute of Harvard and MIT||Institute for Molecular Medicine Finland, University of HelsinkiPsychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard||Harvard Medical School
医学研究方法遗传学基础医学
Cordioli Mattia,Smoller Jordan W.,Feng Yen-Chen A.,FinnGen,Neale Benjamin M.,Ganna Andrea,Ge Tian.Findings and insights from the genetic investigation of age of first reported occurrence for complex disorders in the UK Biobank and FinnGen[EB/OL].(2025-03-28)[2025-06-03].https://www.medrxiv.org/content/10.1101/2020.11.20.20234302.点此复制
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