Pleiotropy between neuroticism and physical and mental health: findings from 108 038 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 (β between 0.009-0.043), and in a negative direction in the case of body mass index (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.
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 General Hospital, Southampton, UK.
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CR
Gale
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.
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SP
Hagenaars
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
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Davies
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
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WD
Hill
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
D C M
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Liewald
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
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B
Cullen
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
B W
BW
Penninx
Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
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DI
Boomsma
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
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J
Pell
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
A M
AM
McIntosh
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
D J
DJ
Smith
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
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IJ
Deary
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
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Harris
D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D058685:Genetic Pleiotropy / Q000235:genetics*; D055106:Genome-Wide Association Study; D006304:Health Status; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D000075384:Neuroticism; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology