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 an 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 ischaemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and Type 2 diabetes mellitus (T2DM). Methods and results 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 aetiology of cardiometabolic diseases in the main analyses, followed by several sensitivity analyses for robustness validation. Genetically predicted self-reported daytime napping [T2DM: OR, 1.56 (95% confidence interval, 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 an 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. Conclusion 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.