Assessing causality between mitochondrial-associated proteins with musculoskeletal diseases: A Mendelian
Jia-Chen Li1,2, Wei-Sheng Huang2, Da-Hang Yang1
1Department of Orthopedics, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Medicine
|March 11, 2025
Summary
Mitochondrial proteins COA3 and COX4I2 may protect against osteoarthritis (OA), while SLC25A18 is a risk factor for rheumatoid arthritis (RA), according to Mendelian randomization analysis.
Area of Science:
- Genetics
- Cellular Biology
- Rheumatology
Background:
- Musculoskeletal diseases are a major cause of disability.
- Mitochondria are crucial for cellular energy and function.
- Mitochondrial roles in musculoskeletal disease pathogenesis are not fully understood.
Purpose of the Study:
- To investigate causal links between mitochondrial functions and musculoskeletal diseases.
- To analyze osteoarthritis (OA), osteoporosis, rheumatoid arthritis (RA), and ankylosing spondylitis.
- To use Mendelian randomization (MR) for genetic evidence.
Main Methods:
- Systematic data retrieval from IEU OpenGWAS and UK Biobank.
- Utilized single nucleotide polymorphisms (SNPs) as instrumental variables.
- Employed inverse variance weighting and various MR sensitivity analyses.
Main Results:
- Identified 14 mitochondrial functional proteins.
- COA3 and COX4I2 showed a protective causal effect on OA.
- SLC25A18 demonstrated a causal relationship as a risk factor for RA.
Conclusions:
- Provides genetic evidence for COA3, COX4I2, and SLC25A18 in OA and RA.
- Suggests specific mitochondrial proteins influence musculoskeletal disease development.
- Informs potential prevention and treatment strategies for OA and RA.
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