Identification of blood metabolites linked to the risk of intervertebral disc diseases: a comprehensive Mendelian randomization study

Intervertebral disc degeneration (IVDD) has affected millions of people worldwide and dramatically affects human beings' quality of life. Observational studies hypothesize that metabolites play key roles as markers and effectors of IVDD, but their causality has not yet been illustrated.We conducted comprehensive Mendelian randomization (MR) to determine the causal relationship between 249 plasma metabolites and IVDD. Inverse-variance weighting was used as the primary estimate, whereas MR-Egger and weighed median were used to detect robustness. A series of sensitivity analyses including Cochran Q test, leave one out, and MR-Egger intercept analysis were also conducted.In total, we found 13 blood metabolites significantly associated with IVDD, including phospholipids in very large high-density lipoprotein (HDL), free cholesterol to total lipids ratio in very large HDL, average diameter for HDL particles, cholesteryl esters to total lipids ratio in large HDL, free cholesterol to total lipids ratio in medium HDL, creatinine, free cholesterol to total lipids ratio in large HDL, phospholipids to total lipids ratio in very large HDL, cholesterol to total lipids ratio in very large HDL, cholesteryl esters to total lipids ratio in large HDL, phospholipids in large HDL, total lipids in very large HDL, and total lipids in large HDL. No pleiotropy was detected. Heterogeneity existed in several estimates and random-effect inverse-variance weighting was applied.Our study highlighted the causal association of blood metabolites with the risk of IVDD. Our results provide new insights into possible treatment protocols controlling the concentration of specific blood metabolites in IVDD patients. Key messages What is already known on this topic Low back pain is the most common symptom for patients with intervertebral disc degeneration (IVDD) and influences the quality of life of large populations. Observational studies have indicated the association between metabolites and IVDD. However, causality has not been determined yet. What this study adds We conducted a comprehensive Mendelian randomization study to reveal the causal effect from 249 blood metabolites on low back pain. A total of 13 metabolites were found to causally affect the risk of IVDD, among which 11 were negatively associated and 2 were positively asscociated. How this study might affect research, practice, or policy These 13 significant metabolites could serve as biomarkers for IVDD and our results provide new insights into possible treatment protocols for IVDD patients.