Self-reported daytime napping, daytime sleepiness, and other sleep phenotypes in the development of cardiometabolic diseases: a Mendelian randomization study

Abstract

Aims Sleep disorders are associated with increased risk of cardiometabolic diseases in observational studies, but the causality remains unclear. In this study, we leveraged two-sample Mendelian randomization (MR) analyses to assess the causal associations of self-reported daytime napping, daytime sleepiness, and other sleep phenotypes with cardiometabolic diseases including ischemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and type 2 diabetes mellitus (T2DM). Methods We selected genetic variants as instrumental variables for self-reported daytime napping, daytime sleepiness, morning person, insomnia, short sleep duration, and long sleep duration from European-descent genome-wide association studies (GWASs). Summary statistics for cardiometabolic diseases originated from four different GWASs with a total of 2,500,086 participants. We used the inverse-variance weighted method to explore the role of self-reported sleep phenotypes on the etiology of cardiometabolic diseases in the main analyses, followed by several sensitivity analyses for robustness validation. Results Genetically predicted self-reported daytime napping (T2DM: OR, 1.56 [95% CI, 1.21-2.02]), insomnia (IS: OR, 1.07 [1.04-1.11]; CAD: OR, 1.13 [1.08-1.17]; HF: OR, 1.10 [1.07-1.14]; T2DM: OR, 1.16 [1.11-1.22]) and short sleep duration (CAD: OR, 1.37 [1.21-1.55]) were causally associated with elevated risk of cardiometabolic diseases. Moreover, genetically determined self-reported daytime sleepiness (CAD: OR, 2.05 [1.18-3.57]; HF: OR, 1.82 [1.15-2.87]) and morning person (HF: 1.06 OR, [1.01-1.11]) had potential detrimental effect on cardiometabolic risks. Conclusions Self-reported daytime napping, insomnia, and short sleep duration had causal roles in the development of cardiometabolic diseases, while self-reported daytime sleepiness and morning person was the potential risk factor for cardiometabolic diseases.

Relations among perceived stress, fatigue, and sleepiness, and their effects on the ambulatory arterial stiffness index in medical staff: A cross-sectional study

“…Moreover, the mean ESS score among our participants was 8.84 points; that it was >6 indicates common daytime sleepiness among these medical staff. Daytime sleepiness is associated with development of cardiometabolic disease (Qureshi et al, 1997;Newman et al, 2000;Jia et al, 2022), consistent with our result and supporting our third hypothesis. In terms of mechanism of action, sleep disorders diminish nitric oxide bioavailability to impair nitric oxide-mediated endothelial-dependent vasodilation, leading to a hardening of the arteries and increased risk of cardiovascular disease (Bain et al, 2017).…”

Potential genetic and epigenetic mechanisms in insomnia: A systematic review

“…In this framework, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal effect on the risk of some mental conditions such as major depression, bipolar disorder type II, schizophrenia, autism spectrum disorder, alcohol, nicotine and opioid use, attention‐deficit/hyperactivity disorder, anxiety and post‐traumatic stress disorder (PTSD), and suicidal behaviours with reverse causality observed for major depression, nicotine use, and PTSD only (Jansen, Dolinoy, et al, 2019, Jansen, Watanabe, et al, 2019; Gao et al, 2019; Song et al, 2020; Pasman et al, 2020; Lewis et al, 2020; Cai et al, 2021; Huang et al, 2021; Carpena et al, 2021; Watanabe et al, 2022; Sun et al, 2022; Baranova et al, 2022; Zhou et al, 2022; Nassan et al, 2022). Similarly, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal one‐way effect on the risk of some medical conditions including: coronavirus disease 2019 (COVID‐19) susceptibility (Peng et al, 2022), cognitive impairment, neurodegenerative conditions (Sun et al, 2020; Zhang et al, 2022), cardiovascular diseases (Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Jia et al, 2022; Liu et al, 2021; Zheng et al, 2020), diabetes, cardio‐metabolic risks (Gao et al, 2020; Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Liu et al, 2021; Liu et al, 2022), increasing the odds of reporting pain conditions (An et al, 2022; Broberg et al, 2021; Chu et al, 2021; Shu et al, 2022) and for other medical conditions (Bao et al, 2022; He et al, 2022; Huo et al, 2021; Zha et al, 2021).…”

The association between daytime napping and risk of type 2 diabetes is modulated by inflammation and adiposity: Evidence from 435 342 UK‐Biobank participants

“…Finally, causality cannot be determined because of the observational nature of this study, and randomized clinical trials are needed to verify our findings. However, we deemed that this criticism could be assuaged to some extent, given that several previous prospective cohort studies and Mendelian randomization have consistently reported positive associations of daytime napping with obesity and T2D but not vice versa, 4,5,7,9,33,34,42,51–53 supporting the causal link being inferred.…”