Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank

Abstract

Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.

Sleeping Late Increases the Risk of Myocardial Infarction in the Middle-Aged and Older Populations

“…Previous studies showed that self-reported sleep duration <6 h was a potential pathogenic factor for MI (8). Genetically determined short sleep duration (<6 h) was also a potential causal risk factor of MI (9). Selfreported sleep duration could be calculated as the length of time from bedtime to wake-up time.…”

Association between dietary fiber intake and atherosclerotic cardiovascular disease risk in adults: a cross-sectional study of 14,947 population based on the National Health and Nutrition Examination Surveys

“…Fourth, some variables related to CVD, such as genetic factors could not be analyzed due to the database limitations. Fifth, mental state and sleep duration were associated with CVD risk [ 36 , 37 ], but we did not analyze the effects of these variables, which may be potentially confounding.…”

Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis: A Prospective Cohort Study of 0.5 Million Participants

“…As for lifestyle factors, earlier studies have shown that insufficient sleep is one of the causes of AVS [ 76 ]. A previous MR analysis in the UK biobank about sleep duration and CVD demonstrated that short sleep duration is a potential causal risk factor for several CVDs [ 76 ].…”

“…As for lifestyle factors, earlier studies have shown that insufficient sleep is one of the causes of AVS [ 76 ]. A previous MR analysis in the UK biobank about sleep duration and CVD demonstrated that short sleep duration is a potential causal risk factor for several CVDs [ 76 ]. Poor sleep quality may affect CVD through pathways, including inflammation, nervous system dysfunction, and metabolic abnormalities [ 77 , 78 , 79 ], indicating that improving sleep quality may prevent CVD development.…”