Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank

Gale, C. E. et al. (2016) Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank. Translational Psychiatry, 6, e791. (doi: 10.1038/tp.2016.56) (PMID:27115122)

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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 UK Biobank and health-related measures from 14 large genome-wide association studies (GWAS). Summary information for the 17 GWAS 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 , and coronary artery disease , and smoking (β between 0.009 – 0.043) and in a negative direction in the case of BMI (β = -0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.

Item Type:Articles
Additional Information: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). We thank Riccardo Marioni for conducting some analyses for this paper. Funding from the BBSRC and the Medical Research Council (MRC) is gratefully acknowledged.
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Cullen, Dr Breda and Pell, Professor Jill
Authors: Gale, C. E., Hagenaars, S. P., Davies, G., Hill, W. D., Liewald, D. C. M., Cullen, B., Pell, J., McIntosh, A. M., Smith, D., Deary, I. J., and Harris, S. E.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Translational Psychiatry
Publisher:Nature Publishing Group
ISSN (Online):2158-3188
Published Online:26 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Translational Psychiatry 6:e791
Publisher Policy:Reproduced under a Creative Commons License

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