Investigation of the Association Between Hyperlipidemia and Ossification of The Posterior Longitudinal Ligament Through Two-Sample Mendelian Randomization Analysis.

Study design: A Two-Sample Mendelian Randomization Analysis.

Objective: This study aimed to investigate the association between genetically predicted hyperlipidemia and ossification of the posterior longitudinal ligament (OPLL) using two-sample Mendelian randomization (MR) analysis.

Summary of background data: Several observational studies suggested associations between hyperlipidemia and OPLL.

Method: Genome-wide association study (GWAS) summary statistics for hyperlipidemia and OPLL were retrieved from the public database. The MR analysis employed the Inverse Variance Weighted (IVW) method, which was supplemented by MR-Egger, weighted median, and weighted mode analyses. Sensitivity analyses, incorporating Cochran's Q test, MR-Egger regression and the MR pleiotropy residual sum and outlier test, additionally assessed the robustness of the findings.

Results: The IVW analysis revealed a significant association between total cholesterol levels and OPLL (OR: 1.44,95% CI:1.06-1.96, P=0.02). Similarly, a significant association was observed between LDL cholesterol and OPLL (OR: 1.31,95%CI:1.05-1.63, P=0.02). Supplementary analyses further supported the significant association of total cholesterol levels and LDL cholesterol on OPLL (P <0.05). In sensitivity analyses, LDL cholesterol exposure showed robust results, with no outliers detected by loo or mrpresso, despite MR-Egger hints at pleiotropy. For total cholesterol exposure, MR-Egger suggested no pleiotropy, though heterogeneity and outliers were present. Outlier removal confirmed the initial positive association, underlining study stability. However, no significant associations were found of hyperlipidemia, triglycerides, HDL cholesterol on OPLL.

Conclusion: This study suggests a association of total cholesterol levels and LDL cholesterol levels on OPLL. Further research is warranted to validate these findings and explore potential therapeutic implications.