Association of insomnia, insulin resistance traits, and cardiovascular disease risk: A two‐step Mendelian randomization study

Aims Insomnia increases the risk of cardiovascular diseases (CVDs), but whether insulin resistance (IR) or its related traits mediate the underlying associations is unclear. We conducted a two‐step two‐sample Mendelian randomization (MR) study to address these questions. Methods and Results We selected genetic variants of insomnia, IR, and its traits as instrumental variables, whereas summary‐level data of five CVDs served as the main outcomes, which were derived from previous genome‐wide association studies. In the MR analysis, genetically predicted insomnia symptoms were significantly associated with five CVD risks and six IR‐related traits after correcting for multiple tests, whereas genetically predicted IR and its related traits, such as T2DM, TG, and high‐density lipoprotein cholesterol (HDL‐C), were associated with four CVD risks. In the mediation analysis, we found strong evidence for the mediating effects of IR, TG, HDL‐C, and T2DM in the causal pathway from insomnia to four CVDs, except for atrial fibrillation. The multivariable MR analysis provided further evidence supporting the potential mediation effects of IR and its related traits in the causal pathway between insomnia and CVDs. Conclusions These results suggest that genetically predicted insomnia symptoms are associated with a higher risk of CVDs, with considerable mediation by IR and T2DM.