Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia

Hagenaars, S.P. et al. (2016) Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia. Molecular Psychiatry, 21, pp. 1624-1632. (doi: 10.1038/mp.2015.225) (PMID:26809841) (PMCID:PMC5078856)

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.

• Item Type: Articles
• Additional Information: <br>METASTROKE Consortium, International Consortium for Blood Pressure GWAS, SpiroMeta Consortium, CHARGE Consortium Pulmonary Group, CHARGE Consortium Aging and Longevity Group.</br> <br>This research has been conducted using the UK Biobank Resource. The work was undertaken in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/ K026992/1). Funding from the BBSRC and Medical Research Council (MRC) is gratefully acknowledged.</br>
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel and Cullen, Dr Breda and Ritchie, Dr Stuart and Pell, Professor Jill
• Authors: Hagenaars, S.P., Harris, S.E., Davies, G., Hill, W.D., Liewald, D.C.M., Ritchie, S. J., Marioni, R.E., Fawns-Ritchie, C., Cullen, B., Malik, R., Worrall, B.B., Sudlow, C.L.M., Wardlaw, J.M., Gallacher, J., Pell, J., McIntosh, A.M., Smith, D.J., Gale, C.R., and Deary, I.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Molecular Psychiatry
• Publisher: Nature Publishing Group
• ISSN: 1359-4184
• ISSN (Online): 1476-5578
• Published Online: 26 January 2016
• Copyright Holders: Copyright © 2016 Macmillan Publishers
• First Published: First published in Molecular Psychiatry 21:1624-1632
• Publisher Policy: Reproduced under a Creative Commons licence