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Pleiotropy between neuroticism and physical and mental health: findings from 108038 men and women in UK Biobank

Pleiotropy between neuroticism and physical and mental health: findings from 108038 men and women in UK Biobank
Pleiotropy between neuroticism and physical and mental health: findings from 108038 men and women in UK Biobank
People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108?038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (? between 0.009-0.043), and in a negative direction in the case of body mass index (?=-0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
1-7
Gale, C.R.
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Hagenaars, S.P.
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Davies, G.
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Hill, W.D.
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Liewald, D.C.M.
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Cullen, B.
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Penninx, B.W.
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CHARGE consortium Aging & Longevity Group, [Unknown]
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Boomsma, D.I.
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Pell, J.
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McIntosh, A.M.
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Smith, D.J.
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Deary, I.J.
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Harris, S.E.
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Gale, C.R.
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Hagenaars, S.P.
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Davies, G.
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Hill, W.D.
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Liewald, D.C.M.
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Cullen, B.
f0c31066-2c9d-4122-b62f-549314590a67
Penninx, B.W.
0dc054d8-13b4-41b9-a27a-cc81ddc2639f
CHARGE consortium Aging & Longevity Group, [Unknown]
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Boomsma, D.I.
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Pell, J.
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McIntosh, A.M.
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Smith, D.J.
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Deary, I.J.
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Harris, S.E.
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Gale, C.R., Hagenaars, S.P., Davies, G., Hill, W.D., Liewald, D.C.M., Cullen, B., Penninx, B.W., CHARGE consortium Aging & Longevity Group, [Unknown], Boomsma, D.I., Pell, J., McIntosh, A.M., Smith, D.J., Deary, I.J. and Harris, S.E. (2016) Pleiotropy between neuroticism and physical and mental health: findings from 108038 men and women in UK Biobank. Translational Psychiatry, 6 (e791), 1-7. (doi:10.1038/tp.2016.56). (PMID:27115122)

Record type: Article

Abstract

People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108?038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (? between 0.009-0.043), and in a negative direction in the case of body mass index (?=-0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.

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Accepted/In Press date: 6 March 2016
e-pub ahead of print date: 26 April 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 393532
URI: http://eprints.soton.ac.uk/id/eprint/393532
PURE UUID: 9e4a9387-1002-4439-880e-1b070d69414d
ORCID for C.R. Gale: ORCID iD orcid.org/0000-0002-3361-8638

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Date deposited: 28 Apr 2016 13:12
Last modified: 18 Feb 2021 16:44

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Contributors

Author: C.R. Gale ORCID iD
Author: S.P. Hagenaars
Author: G. Davies
Author: W.D. Hill
Author: D.C.M. Liewald
Author: B. Cullen
Author: B.W. Penninx
Author: [Unknown] CHARGE consortium Aging & Longevity Group
Author: D.I. Boomsma
Author: J. Pell
Author: A.M. McIntosh
Author: D.J. Smith
Author: I.J. Deary
Author: S.E. Harris

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