• World Neurosurg · Feb 2025

    Causal relationship between mitochondrial DNA copy number and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study.

    • Chengjie Ma, Junhua Fang, Rui Xu, Langtao Ma, Guiqian Zhang, Xionggang Yang, Zhi Peng, and Sheng Lu.
    • Orthopaedics Department, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, The Key Laboratory of Digital Orthopaedics of Yunnan Provincial, Yunnan Provincial Center for Clinical Medicine in Spinal and Spinal Cord Disorders, Kunming, China, 650000, China.
    • World Neurosurg. 2025 Feb 11: 123732123732.

    PurposeThe 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 analyses.MethodsThe causal relationship between mtDNA-CN and IVDD was estimated using a bidirectional two-sample Mendelian randomization (MR) method. The inverse-variance weighted (IVW) method was employed as the main MR method. Sensitivity analyses were conducted to validate the robustness and reliability of the MR results.ResultsThe MR results by IVW revealed that genetically predicted mtDNA-CN was not associated with IVDD (OR = 0.91, 95% CI = 0.79-1.04, P = 0.1731). Similar results were observed in other four 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 SNP. Moreover, the reverse MR analysis did not reveal any significant causal association of IVDD on mtDNA-CN.ConclusionThe 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. Further research is needed to explore to better understand the underlying mechanisms of this condition.Copyright © 2025. Published by Elsevier Inc.

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