Evaluation relationships between subjective wellbeing, personality traits, and Alzheimer's disease: A two-sample Mendelian randomization study

Observational studies have suggested that subjective wellbeing and personality traits link to risk of Alzheimer's disease (AD), but it is unclear if these associations are causal. Methods: We performed two-sample Mendelian randomization to assess potential causality. Genetic associations were obtained from the largest genome-wide association studies in Social Science Genetic Association Consortium (N = 298,420), Genetics of Personality Consortium (N = 81,036), and four independent consortia of AD (N = 455,258). We run the inverse variance weighted (IVW) approach as one primary analysis. A Bonferroni-corrected threshold of p < 8.33 × 10−3 was considered significant, and p values between 8.33 × 10−3 and 0.05 were considered to be suggestive of an association. The suggestive association with decreased risk of AD was noted for a genetically predicted 1-SD increase in subjective wellbeing (odds ratio = 0.963, 95% confidence interval = 0.930–0.997; p = 0.032). Genetically predicted greater neuroticism was significantly associated with lower subjective wellbeing (β = −0.077; p = 0.004). No putative personality traits were significantly associated with AD risk after correction for multiple tests, including agreeableness (β = −0.0010; p = 0.477), conscientiousness (β = 0.0018; p = 0.270), openness (β = 0.0004; p = 0.738), neuroticism (β = −0.0098; p = 0.262), or extraversion (β = 0.0120; p = 0.262). Subjective wellbeing may independently reduce the risk of AD. Residual confounding is likely to be responsible for the previous observational relationships between personality traits and AD.