No Evidence of a Genetic Causal Relationship between Metabolic Syndrome and Low Back Pain: A Two-Sample Mendelian Randomization Study

Background: To investigate the causal relationship between metabolic syndrome (MetS) and low back pain (LBP) using Mendelian randomization (MR). Methods: A two-sample MR analysis was conducted using summary statistics from a public genetic variation database for a European population. The primary analysis employed the inverse variance weighting method (IVW), with supplementary methods including the weighted median model, MR-Egger, simple model, and weighted model. Cochran’s Q test, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and the leave-one-out (LOO) sensitivity test were applied to assess heterogeneity and pleiotropy of identified instrumental variables (IVs). TwoSampleMR and MR-PRESSO packages in R software conducted all analyses. Results: The IVW method indicated that MetS (OR=1.003, 95%CI=1.002-1.004, P=3.47×10 -6 ) and waist circumference (OR=1.003, 95%CI= 1.002-1.004, P=1.03×10 -6 ) were linked to an increased risk of LBP in the European population. However, the OR was close to 1, suggesting a lack of a causal relationship. No statistically significant association was found between fasting blood glucose (OR= 0.999, 95% CI= 0.997-1.002, P= 0.661), hypertension (OR= 1.005, 95% CI= 0.997-1.013, P= 0.241), triglycerides (OR= 1.000, 95% CI= 0.999-1.001, P= 0.757), high-density lipoprotein cholesterol (OR= 0.999, 95% CI= 0.998-1.000, P= 0.069), and LBP in the European population. The funnel plot was symmetric and LOO sensitivity analysis showed that the results of the MR analysis were not driven by a single SNP. Moreover, no heterogeneity, horizontal pleiotropy or outliers were identified. Conclusions: This MR study does not support a causal relationship between MetS and its components and the risk of LBP.