Causal associations between sleep traits and four cardiac diseases: a Mendelian randomization study

Abstract

Aims: Previous studies investigated the associations between sleep traits and cardiac diseases, but the evidence for the causal inferences was unclear. This study aimed to explore the causal relationship between sleep and cardiac diseases by virtue of Mendelian randomization (MR).

Methods and results: Summary-level data for exposure variables (sleep duration, chronotype, and insomnia) and outcome variables (ischaemic heart disease, atrial fibrillation, myocardial infarction, and heart failure) were derived from UK Biobank. Data from the FinnGen consortium was used as a robustness check. In MR analysis, the inverse variance weighted (IVW) method was applied to infer causality between exposure and outcome. MR-Egger regression was used to identify pleiotropy, and MR-PRESSO outlier test was used to remove the pleiotropy of the genetic instruments. Based on UK Biobank, MR analysis suggested that sleep duration was weakly associated with atrial fibrillation (OR = 0.9999, 95% CI: 0.9998-0.9999) and ischaemic heart disease (OR = 0.9997, 95% CI: 0.9995-0.9998). Insomnia was associated with ischaemic heart disease (OR = 1.0117, 95% CI: 1.0051-1.0183) and myocardial infarction (OR = 1.0049, 95% CI: 1.0019-1.0079). No associations were found between chronotype and cardiac diseases (P > 0.05). We did not find pleiotropy except for insomnia with ischaemic heart disease and myocardial infarction using MR-Egger regression, and MR-PRESSO analysis consistent with IVW. Finally, we obtained the same direction as with UK Biobank using the FinnGen data.

Conclusions: Sleep duration and insomnia might be the potential causal risk factors of cardiac diseases. As the OR was small, these associations are probably not clinically relevant. Further validation studies are needed.

Keywords: Cardiac disease; Causal relationship; Mendelian randomization; Sleep.