TY - JOUR T1 - Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank JF - bioRxiv DO - 10.1101/031138 SP - 031138 AU - Catharine R Gale AU - Saskia P Hagenaars AU - Gail Davies AU - W David Hill AU - David CM Liewald AU - Breda Cullen AU - International Consortium for Blood Pressure GWAS AU - CHARGE consortium Aging and Longevity Group AU - Jill Pell AU - Andrew M McIntosh AU - Daniel J Smith AU - Ian J Deary AU - Sarah E Harris Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/11/10/031138.abstract N2 - There is considerable evidence that people with higher levels of the personality trait 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 12 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 12 large genome-wide association studies (GWAS). Summary information for the 12 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 (β = 0.017), major depressive disorder (β = 0.036), schizophrenia (β = 0.036), and coronary artery disease (β = 0.011), and in a negative direction in the case of BMI (β = −0.0095). These findings indicate that a high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia. ER -