Body mass index and risk of lumbar spondylolisthesis: An observational study based on two-sample Mendelian randomization analysis

This study aims to investigate the potential causal relationship between body mass index (BMI) and lumbar spondylolisthesis through the application of Mendelian randomization (MR) analysis. We utilized comprehensive data derived from large-scale genome-wide association studies to examine the association between BMI and lumbar spondylolisthesis in populations of European ancestry. Independent genetic variants with significant correlations to BMI and lumbar spondylolisthesis were selected as instrumental variables to ensure methodological rigor. To evaluate the causal impact of BMI on the risk of developing lumbar spondylolisthesis, 3 distinct MR approaches were employed: MR-Egger regression, Weighted Median analysis, and inverse variance weighted estimation. Robustness and consistency of the findings were assessed through heterogeneity testing, multiplicity analysis, and a leave-one-out sensitivity evaluation to confirm the stability of the results. The inverse variance weighted analysis revealed a significant positive association between BMI and lumbar spondylolisthesis risk, with an odds ratio of 1.66 and a 95% confidence interval of 1.20 to 2.29 (P = .002). This finding indicates that individuals with higher BMI are more predisposed to developing lumbar spondylolisthesis. Complementary results from heterogeneity and multiplicity assessments demonstrated no evidence of significant heterogeneity or horizontal pleiotropy, reinforcing the reliability of the findings. Furthermore, the leave-one-out sensitivity analysis confirmed the stability and robustness of the results, providing additional validation of the causal relationship. This investigation offers valuable insights by leveraging two-sample Mendelian randomization analysis to explore the causal link between BMI and lumbar spondylolisthesis. The evidence strongly suggests that elevated BMI contributes significantly to the risk of lumbar spine slippage. These findings highlight the importance of weight management as a preventive strategy for lumbar spine disorders. Promoting healthy BMI levels may serve as a critical intervention to mitigate the risk of lumbar spondylolisthesis, emphasizing the necessity for targeted public health initiatives focused on weight control to enhance spinal health and overall well-being.