A Mendelian randomization study investigating the role of sleep traits and their joint effects on the incidence of atrial fibrillation

Abstract

Background and aims: Sleep disturbances can induce alterations in functional and electrical properties of the heart, thereby increasing susceptibility to atrial fibrillation (AF). We aimed to test the causal role of different sleep traits and their joint effects on the risk of AF.

Methods: We used an observational cohort study design along with one-sample and factorial Mendelian randomization (MR) approaches to test for individual and joint associations of sleep traits (i.e., insomnia symptoms, sleep duration and chronotype) on the risk of AF using UK Biobank and the second survey of the Trøndelag Health Study (HUNT2).

Results: One-sample MR analysis showed that genetic predisposition to insomnia symptoms (hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.07, 1.21) and short (≤6 h vs. 7-8 h) sleep duration (HR 1.14; 95% CI 1.04, 1.26) increased the risk of AF in UK Biobank. However these findings (HR 0.95; 95% CI 0.81, 1.11 for insomnia symptoms and HR 1.41; 95% CI 0.57, 3.46 for short sleep duration) were not consistent in HUNT2. Factorial MR analysis showed participants with genetic predisposition to both insomnia symptoms and short sleep duration (HR 1.08; 95% CI 1.03, 1.12) had the highest risk of AF, although there was no evidence of interaction (relative excess risk due to interaction (RERI 0.03; 95% CI -0.03, 0.09). However, this finding (HR 0.96; 95% CI 0.89, 1.04) was not consistent in HUNT2. Participants with genetic predisposition to both a morning chronotype and insomnia symptoms (HR 1.08; 95% CI 1.04, 1.13) and a morning chronotype and short sleep (HR 1.06; 95% CI 1.02, 1.10) had the highest risk of AF in UK Biobank, although there was no evidence of interaction (RERI -0.01; 95% CI -0.07, 0.04 and RERI 0.06; 95% CI -0.01, 0.12, respectively).

Conclusions: Our study indicates that insomnia symptoms and short sleep duration are causal risk factors for AF. However, having two sleep traits in combination does not increase risk beyond the additive risk of each individual trait. This reinforces clinical and public health efforts to effectively manage insomnia symptoms and short sleep, in order to mitigate the risk of AF and improve overall cardiovascular health.

Keywords: Atrial fibrillation; chronotype and Mendelian randomization; insomnia; sleep duration.