Related Experiment Video
Updated: May 20, 2025
Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
Published on: July 8, 2021
Transcriptome Data Combined With Mendelian Randomization Analysis Identifies Key Genes Associated With Mitochondria
Hongfei Nie1, Xiao Hu2, Jiaxiao Wang1
1Department of Pain Management, West China Hospital Sichuan University Chengdu Sichuan Province China.
Background:
Intervertebral disc degeneration (IDD) is a major cause of cervical and lumbar diseases, significantly impacting patients' quality of life. Mitochondria and cell death have been implicated in IDD, but the key related genes remain unknown.
Methods:
Differentially expressed genes (DEGs) between IDD and control samples were identified using GSE70362. Mitochondria-related genes (MRGs) and programmed cell death-related genes (PCDRGs) were intersected with DEGs to find DE-MRGs and DE-PCDRGs. Weighted gene co-expression network analysis (WGCNA) identified key module genes, and the overlap with DEGs revealed candidate genes. Mendelian randomization (MR) analysis was used to determine genes causally linked to IDD. Machine learning and expression validation further refined key genes, which were then used to build a nomogram to predict IDD risk. Additionally, gene set enrichment analysis (GSEA), immune infiltration, and single-cell analysis were performed.
Results:
A total of 515 DEGs were intersected with 224 key module genes, yielding 31 candidate genes. Six genes-BCKDHB, BID, TNFAIP6, VRK1, CAB39L, and TMTC1-showed a causal relationship with IDD. BID, TNFAIP6, and TMTC1 were further identified as key genes through machine learning and validation. A nomogram was developed based on these genes. GSEA revealed BID and TMTC1 were enriched in N-glycan biosynthesis, TNFAIP6 and TMTC1 in aminoacyl tRNA biosynthesis, and BID and TMTC1 in ribosomal pathways. Activated dendritic cells, CD56dim natural killer cells, monocytes, and other immune cells were elevated in IDD, with TNFAIP6 strongly correlating with activated dendritic cells. Key genes were expressed at higher levels in degraded samples.
Conclusion:
BID, TMTC1, and TNFAIP6 were identified as key genes linked to mitochondria and cell death in IDD, offering new insights for diagnosis and treatment.
