Abstract
Both short (<7 h per night) and long (≥9 h per night) sleep durations are related to atrial fibrillation (AF) and heart failure (HF), but their causality has not been confirmed. We applied Mendelian randomization (MR) approaches to estimate the causal association between genetically determined sleep duration and the risk of AF and HF. We performed two-sample MR analysis to obtain the effect of sleep duration on AF and HF. Instrumental variables were constructed using genetic variants known to be associated with continuous sleep duration, short sleep duration, and long sleep duration. MR estimates of the effect of sleep duration on AF and HF were derived based on two large meta-analyses of genome-wide association studies. The pooled MR estimate demonstrated a significant protective effect of continuous sleep duration on HF [odds ratio (OR) = 0.765, 95% confidence interval (CI) = 0.675–0.867; P = 2.64 × 10–5] and a suggestive inverse association of continuous sleep duration with AF (OR = 0.893, 95% CI = 0.804–0.991; P = 0.034). In addition, the results showed a suggestive detrimental effect of short sleep duration on the risk of AF (OR = 1.108, 95% CI = 1.017–1.207; P = 0.019) and HF (OR = 1.136, 95% CI = 1.025–1.258; P = 0.015). Conversely, there is no significant evidence for the causal protective effect of long sleep duration on AF (OR = 0.956, P = 0.410) and HF (OR = 0.921, P = 0.202). This MR study indicated that genetically determined continuous sleep duration has a significant protective effect on HF and a suggestive inverse association with AF. Short sleep duration is positively associated with the risk of AF and HF. Nevertheless, there is no significant evidence for the causal protective effect of long sleep duration on AF and HF. Larger intervention studies are required to confirm the effectiveness of improving sleep on reducing the incidence of AF and HF.
Highlights
Disturbed sleep is prevalent in a modern society (Akerstedt and Nilsson, 2003)
In our Mendelian randomization (MR) analysis, the genetic variant qualified as a valid instrument for causal inference must satisfy the following three essential assumptions: (1) genetic variants must be strongly associated with the exposure; (2) genetic variants should be independent of any other confounders; and (3) genetic variants influence risk of the outcome (AF and heart failure (HF)) only through the exposure (Figure 1)
The use of self-reported rather than objective sleep duration assessment (Matthews et al, 2018) and selection of relatively healthy participants into UKB, which might induce collider bias (Fry et al, 2017). This MR study indicated that genetically determined continuous sleep durations have a significant protective effect on HF and a suggestive inverse association with atrial fibrillation (AF)
Summary
Disturbed sleep is prevalent in a modern society (Akerstedt and Nilsson, 2003). It is well known that poor sleep quality is associated with increased risk of various health problems, such as obesity (Wu et al, 2014), diabetes mellitus (Cappuccio et al, 2010), hypertension (Gangwisch et al, 2006), cardiovascular diseases (Covassin and Singh, 2016; Li et al, 2020), renal disease (Geng et al, 2019), dementia (Fan et al, 2019), metabolic syndrome (Song et al, 2016), and other chronic health conditions (Stenholm et al, 2019). Because of difficulty in disentangling causal from spurious effects due to confounding and reverse causation, randomized clinical trials investigating the association between sleep duration and AF and HF would be difficult. Mendelian randomization (MR) approach has been widely used in estimating the causal effect of clinical factors with diseases. With the application of MR approach, associations between sleep duration and coronary artery disease (CAD), myocardial infarction (MI), and stroke have been demonstrated. Daghlas et al (2019) supported short sleep duration as a potentially causal risk factor for CAD and MI, whereas Zhuang et al (2020) found no significant association between sleep duration with stroke. The aims of the current study were to estimate the effects of genetically determined sleep duration on the risk of AF and HF with MR analysis. We reported results for the associations between sleep duration and ischemic stroke (IS) and its subtypes
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