[A Mendelian randomization study on the relationship between insomnia and osteoporosis]

Objective: To explore the relationship between insomnia and osteoporosis. Methods: Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio (OR) and 95% confidence interval (CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran's Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results: The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% (OR=1.007, 95%CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs (Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10^-5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results (P=0.059), and radial MR did not detect any outliers. Conclusion: Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.