Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

ABSTRACT

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR 1.05; 95% CI 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.