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Updated: May 28, 2025
Measuring Single-Cell Mitochondrial DNA Copy Number and Heteroplasmy Using Digital Droplet Polymerase Chain Reaction
Published on: July 12, 2022
Causal Relationship Between Mitochondrial DNA Copy Number and Intervertebral Disc Degeneration: A Bidirectional
Chengjie Ma1, Junhua Fang1, Rui Xu1
1Department of Orthopedics, 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 Province, the Clinical Medicine Center of Spinal and Spinal Cord Disorders of Yunnan Province, Kunming, China.
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. Further research is needed to explore to better understand the underlying mechanisms of this condition.
Insights
Mitochondrial DNA copy number (mtDNA-CN) does not causally influence intervertebral disc degeneration (IVDD). This Mendelian randomization study found no evidence that mtDNA-CN affects IVDD risk or vice versa.
Area of Science:
- Genetics
- Biochemistry
- Orthopedics
Background:
- Mitochondrial DNA copy number (mtDNA-CN) is implicated in various cellular processes.
- Intervertebral disc degeneration (IVDD) is a common cause of low back pain.
- The potential causal link between mtDNA-CN and IVDD is not well-established.
Purpose of the Study:
- To investigate the potential causal relationship between mtDNA-CN and IVDD.
- To utilize Mendelian randomization (MR) analyses for robust causal inference.
- To explore the bidirectional relationship between mtDNA-CN and IVDD.
Main Methods:
- Bidirectional 2-sample Mendelian randomization (MR) analysis.
- Inverse-variance weighted (IVW) method as the primary analysis.
- Sensitivity analyses including heterogeneity and pleiotropy assessments, and leave-one-out analysis.
Main Results:
- No significant causal association was found between genetically predicted mtDNA-CN and IVDD risk (OR = 0.91, P = 0.1731).
- Reverse MR analysis also showed no significant causal effect of IVDD on mtDNA-CN.
- Sensitivity analyses confirmed the robustness of the findings, with no evidence of horizontal pleiotropy.
Conclusions:
- This study provides no evidence for a causal relationship between mtDNA-CN and IVDD in either direction.
- The findings suggest that genetic factors influencing mtDNA-CN do not play a direct causal role in the development of IVDD.
- Further research is warranted to elucidate the complex interplay of genetic and environmental factors in IVDD pathogenesis.
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