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PMID: 26809841 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular psychiatry ·Vol. 21 ·No. 11 ·2016-00-00 ·Pages 1624-1632

Hagenaars SP, Harris SE, Davies G, Hill WD, Liewald DC, Ritchie SJ, Marioni RE, Fawns-Ritchie C, Cullen B, Malik R, METASTROKE Consortium, International Consortium for Blood Pressure GWAS, SpiroMeta Consortium, CHARGE Consortium Pulmonary Group, CHARGE Consortium Aging and Longevity Group, Worrall BB, Sudlow CL, Wardlaw JM, Gallacher J, Pell J, McIntosh AM, Smith DJ, Gale CR, Deary IJ

Abstract

Causes of the well-documented association between low levels of cognitive functioning 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 and to the method of linkage disequilibrium score 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, body mass index, 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.

MeSH Terms
Adult Aged Biological Specimen Banks Cognition/physiology Databases, Factual Female Genetic Association Studies/methods Genetic Predisposition to Disease/genetics Genome-Wide Association Study/methods Health Humans Linkage Disequilibrium/genetics Male Mental Health Middle Aged Multifactorial Inheritance/genetics Polymorphism, Single Nucleotide/genetics
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Hagenaars S P
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK. | Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Harris S E
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Davies G
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Hill W D
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Liewald D C M
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Ritchie S J
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Marioni R E
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK. | Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Fawns-Ritchie C
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Cullen B
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Malik R
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
METASTROKE Consortium, International Consortium for Blood Pressure GWAS
SpiroMeta Consortium
CHARGE Consortium Pulmonary Group, CHARGE Consortium Aging and Longevity Group
Worrall B B
Department of Neurology, University of Virginia, Charlottesville, VA, USA. | Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Sudlow C L M
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK. | Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Wardlaw J M
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Gallacher J
Department of Psychiatry, University of Oxford, Oxford, UK.
Pell J
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
McIntosh A M
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Smith D J
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Gale C R
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK. | MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Deary I J
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. | Department of Psychology, University of Edinburgh, Edinburgh, UK.
Conflict of Interest

IJD is a participant in UK Biobank. The remaining authors declare no conflict of interest.

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Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
DOI
10.1038/mp.2015.225
Published
2016-00-00
Epub
2016-00-26
Pages
1624-1632
Language
English
Region
England
NLM ID
9607835
PMCID
PMC5078856
Subset
IM
Grants
Medical Research Council · MC_UP_A620_1015 · United Kingdom
Wellcome Trust · 104036 · United Kingdom
Medical Research Council · MC_QA137853 · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
Medical Research Council · MR/K026992/1 · United Kingdom
NHLBI NIH HHS · R01 HL105756 · United States
Medical Research Council · MR/L023784/1 · United Kingdom
Medical Research Council · MR/L023784/2 · United Kingdom
Medical Research Council · MC_UU_12011/2 · United Kingdom
Wellcome Trust · 093707 · United Kingdom
External Links
PubMed source DOI: 10.1038/mp.2015.225 PMC Full Text View journal details
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