Lipids and Lipid-Lowering Drugs With Risk of Intervertebral Disc Degeneration: A Mendelian Randomization Study.

This study examined whether circulating lipid traits and lipid-lowering drug targets are causally associated with intervertebral disc degeneration (IVDD) using a Mendelian randomization (MR) framework. We analyzed summary-level data from genome-wide association studies (GWASs) covering apolipoproteins, lipid parameters, and IVDD. Univariable analysis revealed that inherently elevated high-density lipoprotein cholesterol (HDL-C) correlated with reduced IVDD susceptibility. By contrast, low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein A-I (Apoa-I), and apolipoprotein B (Apob) did not remain significant after Bonferroni correction. Upon adjusting for body mass index (BMI) in a multivariable framework, the protective link between HDL-C and IVDD held strong, whereas LDL-C, TG, and Apob remained nonsignificant. Summary data-based MR and drug-target MR analyses further suggested a significant association between NPC1L1 gene expression and IVDD susceptibility. Overall, these results highlight the potential involvement of lipid pathways in disc degeneration and justify further biological and clinical investigation.