Genetically predicted effects of 10 sleep phenotypes on revision of knee arthroplasty: a mendelian randomization study

Abstract

Abstract Background Accumulating evidence has suggested that sleep disturbances and disorders are common in patients who undergo knee arthroplasty. Revision surgery represents one of the most catastrophic outcomes of knee arthroplasty. However, it remains unclear whether sleep traits are the causes or consequences of knee arthroplasty revision. This study aimed to genetically examine the relationships between sleep traits and knee arthroplasty revision. Methods To determine the causal relationship between sleep traits and knee arthroplasty revision, we employed two-sample Mendelian randomization (MR) using summary statistics from the largest publicly available genome-wide association studies (GWASs). The MR design uses genetic variants as instrumental variables to help separate causal relationships from non-causal associations. The main analyses included an inverse variance weighted (IVW) meta-analysis to obtain primary effect estimates. Sensitivity analyses involving the weighted median approach and MR-Egger regression were also conducted to check for potential pleiotropic biases. Numerous complementary sensitivity analyses were also performed to identify statistically significant causal correlations when there were horizontal pleiotropy and heterogeneity across variants. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Results In the absence of heterogeneity and horizontal pleiotropy, the IVW method revealed that genetically-predicted short sleep duration short sleep duration (average sleep duration of 24 h is 6 h or less) was positively correlated with the risk of knee arthroplasty revision (odds ratio = 1.03, 95% confidence interval = 1.01–1.05, and P = 0.003), while the association between genetically-predicted long sleep duration and knee arthroplasty was negative. The reverse MR analysis did not yield evidence supporting reverse causality relation between knee arthroplasty revision and sleep phenotypes. Conclusion This research indicated that, of the 10 sleep phenotypes we analyzed, only sleep duration was causally associated with knee arthroplasty revision. These discoveries added to the understanding of the role of sleep traits in the etiology of knee arthroplasty revision, which might further expand our insights into the prevention of knee arthroplasty revision.

Keywords

• Mendelian randomization
• Knee arthroplasty revision
• Sleep
• Genome-wide association study
• Causality