Objective: 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.
Results: 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).
Conclusions: 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.
Keywords: Alzheimer's disease; Causality; Mendelian randomization; Personality trait; Subjective wellbeing.
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