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

STUDY DESIGN: A 2-sample Mendelian randomization (MR) analysis. OBJECTIVE: This study aimed to investigate the association between genetically predicted hyperlipidemia and ossification of the posterior longitudinal ligament (OPLL) using a 2-sample MR analysis. BACKGROUND: Several observational studies suggested associations between hyperlipidemia and OPLL. MATERIALS AND METHODS: Genome-wide association study summary statistics for hyperlipidemia and OPLL were retrieved from the public database. The MR analysis employed the inverse variance weighted method, which was supplemented by MR-Egger, weighted median, and weighted mode analyses. Sensitivity analyses, incorporating the Cochran Q test, MR-Egger regression, and the MR pleiotropy residual sum and outlier test, in addition, assessed the robustness of the findings. RESULTS: The inverse variance weighted analysis revealed a significant association between total cholesterol levels and OPLL (odds ratio: 1.44, 95% CI: 1.06-1.96, P = 0.02). Similarly, a significant association was observed between low-density lipoprotein (LDL) cholesterol and OPLL (odds ratio: 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 between hyperlipidemia, triglycerides, and high-density lipoprotein (HDL) cholesterol in OPLL. CONCLUSION: This study suggests an association between total cholesterol levels and LDL cholesterol levels in OPLL. Further research is warranted to validate these findings and explore potential therapeutic implications.