Ce-452780-4 neuroticism and the occurrence of atrial fibrillation: evidence from observational epidemiologic and mendelian randomization

The association between neuroticism and atrial fibrillation (AF) has not been explored. This study aimed to evaluate the epidemiologic and causal relationship between neuroticism and AF. This study included subjects without AF from the UK Biobank nationwide population-based prospective cohort. The 10-year risk of AF, according to the neuroticism score, a summary score based on the self-questionnaire of 12 neurotic behaviour domains, was assessed. The causal relationship between neuroticism and AF was assessed using a two-sample summary-level Mendelian randomization (MR) with the inverse variance weighted (IVW) and weighted-median (WM) method. Among 394,834 participants (aged 56.3 ± 8.1 years, 45.9% male), 23,509 (6.0%) participants were diagnosed with AF during a 10-year follow-up. Female or older age groups were more likely to have higher neuroticism scores compared to male participants with younger ages below 60. The 10-year risk of incident AF significantly increased according to the increase of neuroticism score, after adjusting for possible confounders, including demographic, socioeconomic, lifestyle factors, and comorbidities (adjusted hazard ratio [HR] 1.03 per 1-standard deviation [SD] increase, 95% confidence interval [CI] 1.01-1.05, P<0.001). Among participants who developed AF during follow-up, the AF onset age was significantly younger in those with higher baseline neuroticism scores (onset age 69.7 ± 6.7 years in the lowest neuroticism score group; 66.5 ± 7.6 years in the highest score group). The two-sample MR analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (Odds ratio [OR] by IVW method 1.57, 95% CI [1.01-2.44], P=0.046; OR by WM method 1.57, 95% CI [1.15-2.14], P=0.005) (Figure). A higher level of neuroticism in individuals was causally associated with incident AF and independently predicted AF with earlier onset. Adequate mental health management and lifestyle modification, along with risk factor management of neuroticism, may reduce the future risk of AF.