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

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.

SUBMITTER: Gale CR

PROVIDER: S-EPMC4872414 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Gale C R CR Hagenaars S P SP Davies G G Hill W D WD Liewald D C M DC Cullen B B Penninx B W BW Boomsma D I DI Pell J J McIntosh A M AM Smith D J DJ Deary I J IJ Harris S E SE

Translational psychiatry 20160426

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 correlatio ...[more]

PMID: 27115122

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Project description:Background and objectivesThe association between patterns of physical/mental activity and dementia and how it is affected by disease susceptibility remains unknown. We aimed to examine the association between patterns of physical and mental activity and dementia and whether it can be modified by disease susceptibility to dementia.MethodsIn a prospective cohort study based on UK Biobank, 501,376 dementia-free participants were recruited in 2006-2010 and followed from 1 year after the recruitment date until the end of 2019 for ascertainment of dementia. Data on physical (i.e., physical activity at leisure time, housework-related activity, and transportation) and mental (i.e., intelligence, social contact, and use of electronic device) activity were collected using questionnaires at recruitment. Cox models were used to estimate the associations of physical and mental activity-related items, as well as major activity patterns identified by principal component analysis, with the risk of dementia, adjusted for multiple confounders. The modification role of disease susceptibility on such associations was assessed through stratified analyses by the polygenic risk score (PRS) of dementia generated based on summary statistics of independent genome-wide association studies, by the APOE genotype, and by the self-reported family history of dementia.ResultsThe mean age at recruitment was 56.53, and 45.60% of the participants were male. During a mean follow-up of 10.66 years, 5,185 dementia cases were identified. When analyzed separately, multiple studied items related to physical and mental activity showed significant associations with the risk of dementia. The pattern analyses revealed that a higher level of adherence to activity patterns related to frequent vigorous and other exercises (hazard ratio 0.65, 95% CI 0.59-0.71), housework-related activity (0.79, 0.72-0.85), and friend/family visit (0.85, 0.75-0.96) was associated with a lower risk of dementia. We obtained comparable results for vascular dementia and Alzheimer disease as well as in the stratified analyses by the PRS for dementia, APOE genotype, or family history of dementia.DiscussionActivity patterns more adherent to frequent vigorous and other exercises, housework-related activity, and friend/family visit were associated with a reduced risk of multiple types of dementia. Such associations are independent of disease susceptibility, highlighting the potential of these physical and mental activity patterns, as effective interventions, in the primary prevention of dementia.

Dataset Information

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

Publications

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

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