LAUSR

OBJECTIVE Daytime sleepiness has some association with cardiometabolic diseases and osteoporosis, but it is unknown whether their relationship is causal. This two-sample Mendelian randomization (MR) study aims to explore their causal relationship. MATERIALS AND METHODS We included the largest genome-wide association studies (GWASs) associated with daytime sleepiness, cardiometabolic diseases and osteoporosis. 34 single nucleotide polymorphisms (SNPs) were used as the instrumental variables of daytime sleepiness. RESULTS Genetic predisposition to excessive daytime sleepiness was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.610, 95% confidence interval [CI]: 0.128 to 1.093, standard error [SE]: 0.246, p-value=0.013) and may increase the incidence of type 2 diabetes (beta-estimate: 0.614, 95% CI: 0.009 to 1.219, SE: 0.309, p-value=0.047). We found no causal influence of daytime sleepiness on heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage, forearm bone mineral density (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD). CONCLUSIONS This study suggested that excessive daytime sleepiness was causally associated with increased risk of coronary artery disease, which may benefit to prevent this disease.