Systemic Evaluation of Sleep Duration for Osteoporosis and Cardiometabolic Diseases: A Mendelian Randomization Study

Abstract

Sleep duration suggests some association with osteoporosis and cardiometabolic diseases, but it is unknown if these associations are causal or confounded. In this two-sample Mendelian randomization (MR) study, we included the largest genome-wide association studies (GWASs) associated with sleep duration and the outcome measures of osteoporosis and cardiometabolic diseases. Finally, 25 SNPs associated with short sleep duration and 7 SNPs associated with long sleep duration obtained the genome-wide significance (P<5×10−8) and were used as instrumental variables. Genetic predisposition to short sleep duration was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.199, 95% CI: 0.081 to 0.317, SE:0.060, P-value=0.001) and heart failure (beta-estimate: 0.145, 95% CI: 0.025 to 0.264, SE:0.061, P-value=0.017), which were both confirmed by the sensitivity analyses. Both short and long sleep duration may reduce the estimated bone mineral density (eBMD, beta-estimate: -0.086, 95% CI: -0.141 to -0.031, SE:0.028, P-value=0.002 for short sleep duration; beta-estimate: -0.080, 95% CI: -0.120 to -0.041, SE:0.020, P-value<0.0001 for long sleep duration). There was limited evidence of associations between sleep duration and fracture, type 2 diabetes, atrial fibrillation, fasting glucose, fasting insulin or HbA1c. This study provides robust evidence that short sleep duration is causally associated with low risk of coronary artery disease and heart failure, and suggests that short sleep duration should be avoided to prevent these two cardiovascular diseases. Short and long sleep duration show some MR association with reduced eBMD, which indicates that normal sleep duration may help to prevent osteoporosis. Funding: This study was funded by Foundation of The First Affiliated Hospital of Chongqing Medical University (PYJJ2018-13) and Natural Science Foundation of Chongqing (cstc2019jcyj-msxmX0836). Declaration of Interest: None to declare.