Investigating the causal interplay between sleep traits and risk of acute myocardial infarction: a Mendelian randomization study

Abstract

Background: Few studies have investigated the joint effects of sleep traits on the risk of acute myocardial infarction (AMI). No studies have used factorial Mendelian randomization (MR) which may reduce confounding, reverse causation and measurement error. Thus, it is prudent to study joint effects using robust methods to propose sleep-targeted interventions which lower the risk of AMI. Objective: To investigate the causal interplay between combinations of two sleep traits (including insomnia symptoms, sleep duration or chronotype) on the risk of AMI using factorial MR. Methods: Genetic risk scores for each sleep trait were dichotomized at their median in UK Biobank (UKBB) and the second survey of the Trøndelag Health Study (HUNT2). A combination of two sleep traits constituting 4 groups were analysed to estimate the risk of AMI in each group using a 2x2 factorial MR design. Results: In UKBB, participants with high genetic risk for both insomnia symptoms and short sleep had the highest risk of AMI (HR 1.10; 95% CI 1.03, 1.18), although there was no evidence of any relative excess risk due to interaction (RERI 0.03; 95% CI -0.07, 0.12). These estimates were less precise in HUNT2 (HR 1.02; 95% CI 0.93, 1.13), possibly due to weak instruments. Participants with high genetic risk for both a morning chronotype and insomnia symptoms (HR 1.09; 95% CI 1.03, 1.17); and a morning chronotype and short sleep (HR 1.11; 95% CI 1.04, 1.19) had the highest risk of AMI in UKBB, although there was no evidence of any relative excess risk due to interaction (RERI 0.03; 95% CI -0.06, 0.12; and RERI 0.05; 95% CI -0.05, 0.14, respectively). Chronotype was not available in HUNT2. Conclusions: All combinations of sleep traits increased the risk of AMI except those with long sleep, but the risk from these combinations did not exceed the additive risk from the individual sleep traits.