Causal influence of sleeping phenotypes on the risk of coronary artery disease and sudden cardiac arrest: A Mendelian randomization analysis

Yen-Wei Chiu; Mei-Hsin Su; Yen-Feng Lin; Chia-Yen Chen; Tzu-Ting Chen; Shi-Heng Wang

doi:10.1016/j.sleh.2023.05.009

Causal influence of sleeping phenotypes on the risk of coronary artery disease and sudden cardiac arrest: A Mendelian randomization analysis

Sleep Health. 2023 Oct;9(5):726-732. doi: 10.1016/j.sleh.2023.05.009. Epub 2023 Jul 8.

Authors

Yen-Wei Chiu¹, Mei-Hsin Su², Yen-Feng Lin³, Chia-Yen Chen⁴, Tzu-Ting Chen³, Shi-Heng Wang⁵

Affiliations

¹ Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
² College of Public Health, China Medical University, Taichung, Taiwan.
³ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
⁴ Biogen, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ College of Public Health, China Medical University, Taichung, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Zhunan, Taiwan. Electronic address: shwang@nhri.edu.tw.

PMID: 37429813
DOI: 10.1016/j.sleh.2023.05.009

Abstract

Objectives: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study.

Methods: We used summary statistics of 5 sleep and circadian traits for genome-wide association studies, including chronotype, sleep duration, long sleep (≥9 h a day), short sleep (<7 h a day), and insomnia (sample size range: 237,622-651,295). Coronary artery disease genome-wide association studies with 60,801 cases and 123,504 controls, sudden cardiac arrest genome-wide association studies with 3939 cases and 25,989 controls, and obesity genome-wide association studies with 806,834 individuals were also used. Multivariable Mendelian randomization was performed to estimate the causality.

Results: After adjusting for obesity, genetically predicted short sleep (odds ratio = 1.87 and p = .02), and genetically predicted insomnia (odds ratio = 1.17 and p = .001) were causally associated with increased odds of coronary artery disease. Genetically predicted long sleep (odds ratio = 0.06 and p = .02) and genetically predicted longer sleep duration (odds ratio = 0.36 for per-hour increase in sleep duration and p = .0006) were causally associated with decreased odds of sudden cardiac arrest.

Conclusions: The findings of this Mendelian randomization study indicate that insomnia and short sleep contribute to the development of coronary artery disease, whereas a longer sleep duration protects from sudden cardiac arrest, independent of the influence of obesity. The mechanisms underlying these associations warrant further investigation.

Keywords: Chronotype; Coronary artery disease; Insomnia; Mendelian randomization; Sleep duration; Sudden cardiac arrest.