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

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. (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 11: 1624-1632. doi:10.1038/mp.2015.225


Author 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.
Deary, I. J.
Title Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia
Formatted title
Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
1359-4184
Publication date 2016-11-01
Sub-type Article (original research)
DOI 10.1038/mp.2015.225
Open Access Status DOI
Volume 21
Issue 11
Start page 1624
End page 1632
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 093707
104036
R01 HL105756
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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