{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:08:23Z","timestamp":1764194903485,"version":"3.41.2"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2023YFS0255"],"award-info":[{"award-number":["2023YFS0255"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Differentially expressed genes (DEGs) between IDD and control samples were identified using GSE70362. Mitochondria\u2010related genes (MRGs) and programmed cell death\u2010related genes (PCDRGs) were intersected with DEGs to find DE\u2010MRGs and DE\u2010PCDRGs. Weighted gene co\u2010expression 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\u2010cell analysis were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 515 DEGs were intersected with 224 key module genes, yielding 31 candidate genes. Six genes\u2014BCKDHB, BID, TNFAIP6, VRK1, CAB39L, and TMTC1\u2014showed 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\u2010glycan 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BID, TMTC1, and TNFAIP6 were identified as key genes linked to mitochondria and cell death in IDD, offering new insights for diagnosis and treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70057","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T21:57:26Z","timestamp":1742939846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptome Data Combined With Mendelian Randomization Analysis Identifies Key Genes Associated With Mitochondria and Programmed Cell Death in Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"8","author":[{"given":"Hongfei","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Pain Management, West China Hospital Sichuan University  Chengdu Sichuan Province 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