Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia
Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia
Abstract The causes of the known associations between poorer cognitive function and many adverse neuropsychiatric outcomes, poorer physical health, and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric, and cognitive traits in the participants of UK Biobank, a very large population-based sample (N = 112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics applied to the method of linkage disequilibrium regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer’s disease, schizophrenia, autism, major depressive disorder, BMI, intracranial volume, infant head circumference, and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.
Sudlow Cathie LM、Harris Sarah E、Liewald David CM、Ritchie Stuart J、Cullen Breda、International Consortium for Blood Pressure GWAS、Worrall Bradford B、Wardlaw Joanna M、Pell Jill、Gale Catharine R、Gallacher John、Deary Ian J、Smith Daniel J、Hill W David、McIntosh Andrew M、Davies Gail、Fawns-Ritchie Chloe、CHARGE consortium Aging and Longevity Group、Marioni Riccardo E、Malik Rainer、METASTROKE consortium、SpiroMeta consortium、CHARGE consortium Pulmonary Group、Hagenaars Saskia P
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine||Centre for Clinical Brain Sciences, University of EdinburghCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular MedicineCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghInstitute of Health and Wellbeing, University of GlasgowUniversity of Virginia Departments of Neurology and Public Health SciencesCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Centre for Clinical Brain Sciences, University of EdinburghInstitute of Health and Wellbeing, University of GlasgowCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of Edinburgh||MRC Lifecourse Epidemiology Unit, University of SouthamptonDepartment of Psychiatry, University of OxfordCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghInstitute of Health and Wellbeing, University of GlasgowCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghDivision of Psychiatry, University of EdinburghCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of EdinburghCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine||Queensland Brain Institute, The University of QueenslandInstitute for Stroke and Dementia Research, Klinikum der Universit?t M¨1nchenCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh||Department of Psychology, University of Edinburgh||Division of Psychiatry, University of Edinburgh
遗传学神经病学、精神病学基础医学
Sudlow Cathie LM,Harris Sarah E,Liewald David CM,Ritchie Stuart J,Cullen Breda,International Consortium for Blood Pressure GWAS,Worrall Bradford B,Wardlaw Joanna M,Pell Jill,Gale Catharine R,Gallacher John,Deary Ian J,Smith Daniel J,Hill W David,McIntosh Andrew M,Davies Gail,Fawns-Ritchie Chloe,CHARGE consortium Aging and Longevity Group,Marioni Riccardo E,Malik Rainer,METASTROKE consortium,SpiroMeta consortium,CHARGE consortium Pulmonary Group,Hagenaars Saskia P.Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/031120.点此复制
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