Exploring the direct or mediating associations between lipids, atherosclerosis, obesity, and intervertebral disc degeneration: a Mendelian randomization study

Objective: The aim of this study was to investigate whether there is a causal relationship between different lipids and intervertebral disc degeneration, and to verify whether obesity and atherosclerosis mediate the relationship between lipids and intervertebral disc degeneration. Methods Instrumental variables and their associated data were extracted from the corresponding genome-wide association studies. Inverse variance weighted (IVW), Weighted Median Estimator (WME), MR-Egger regression method, Simple mode (SM) method, Leave-One-Out method and Weighted Mode (WM) method were used to perform Mendelian randomization (MR) statistical analysis of the instrumental variables of exposure and outcome, Sensitivity analyses were then performed using Cochrane's Q value and MR − Egger intercept. Results In the two-sample MR Analysis, HDL, ApoA-1 were protective for both cervical disc degeneration (CDD) and non-cervical disc degeneration (NCDD), BMI contributed to both CDD and NCDD, while AS only contributed to NCDD. In the multivariate MR Analysis, the protective effects of HDL and ApoA-1 on CDD and NCDD were not independent of each other, Meanwhile, AS and BMI were independent risk factors for NCDD. In mediating MR Analysis, both AS and BMI mediated the effect of HDL on NCDD (AS 32.58%, BMI 15.49%), both AS and BMI mediated the effect of ApoA-1 on NCDD (AS 19.35%, BMI 17.65%). Conclusion HDL, ApoA-1, BMI are causally associated with both CDD and NCDD. The protective effects of HDL and ApoA-1 on intervertebral disc degeneration were not independent of each other. AS is causally associated with NCDD. BMI and AS are independent association factors for NCDD. BMI and AS also play important mediating roles in NCDD.