Causal Relationship Between Mitochondrial DNA Copy Number and Intervertebral Disc Degeneration: A Bidirectional 2-Sample Mendelian Randomization Study

作者：Chengjie Ma, Junhua Fang, Rui Xu, Langtao Ma, Guiqian Zhang, Xiong‐gang Yang, Zhi Peng, Sheng Lu · 发表于：World Neurosurgery · 年份：2025 · DOI：10.1016/j.wneu.2025.123732 · 被引用次数：2 · 研究领域：Spine and Intervertebral Disc Pathology、Cervical and Thoracic Myelopathy、Connective tissue disorders research

OBJECTIVE: The causal relationship between mitochondrial DNA copy number (mtDNA-CN) and intervertebral disc degeneration (IVDD) remains unclear. The study aimed to investigate the causal relationship between mtDNA-CN and IVDD using Mendelian randomization (MR) analyses. METHODS: The causal relationship between mtDNA-CN and IVDD was estimated using a bidirectional 2-sample MR method. The inverse-variance weighted method was employed as the main MR method. Sensitivity analyses were conducted to validate the robustness and reliability of the MR results. RESULTS: The MR results by inverse-variance weighted revealed that genetically predicted mtDNA-CN was not associated with IVDD (odds ratio = 0.91; 95% confidence interval = 0.79-1.04; P = 0.1731). Similar results were observed in other 4 MR methods (P > 0.05). Heterogeneity was found in the analysis of IVDD on mtDNA-CN (P < 0.05), while no horizontal pleiotropy was observed (P > 0.05). Furthermore, the leave-one-out analysis indicated the robustness of MR results not biased by a single nucleotide polymorphism. Moreover, the reverse MR analysis did not reveal any significant causal association of IVDD on mtDNA-CN. CONCLUSIONS: The study revealed that there is no causal relationship of mtDNA-CN on the risk of IVDD, nor does IVDD have a significant causal effect on mtDNA-CN. Although the study did not find a significant causal relationship, it provides valuable insights into the complex interplay between genetic factors and IVDD. Fu...