{
  "abstract": "Background: Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell dysfunction, inflammatory remodeling, and oxidative stress. Genetic support for circulating protein signals and their cell-type-specific context remains incompletely defined.\n\nMethods: We integrated deCODE cis-pQTL data with FinnGen R12 M13_INTERVERTEB and human NP scRNA-seq (GSE153066). Local MR screening used harmonized variants with Benjamini–Hochberg correction. The scRNA-seq analysis retained 70,622 cells from 16 libraries and used library-level pseudobulk comparisons. A qPCR validation experiment in PMA-differentiated THP-1 cells (ATCC TIB-202) evaluated MST1, SAA1, BPI, and GCLM under an inflammatory condition.\n\nResults: Four multi-SNP signals passed correction: MST1 showed higher endpoint odds (OR = 1.057, q = 4.15 × 10−6), whereas DLK1 (OR = 0.933, q = 0.016), ITIH1 (OR = 0.926, q = 0.016), and SAA1 (OR = 0.927, q = 0.023) showed inverse associations. TP53I3 and BPI remained nominal exploratory signals. TFRC showed a BH-positive single-SNP result (OR = 1.471, q = 0.023). ScRNA-seq resolved eight broad cell populations and demonstrated between-library heterogeneity; nominal macrophage-composition and selected expression differences did not survive within-panel correction. In the qPCR experiment, relative expression was 1.34 for MST1, 0.31 for SAA1, 3.46 for BPI, and 1.70 for GCLM (control = 1.0; n = 4 independent biological replicates/group; all Welch P < 0.001), consistent with the scRNA-seq directions.\n\nConclusions: The study identifies genetically supported protein signals and ferroptosis-related cellular expression patterns while separating genetic screening from transcriptomic localization. The qPCR experiment provides orthogonal experimental support for selected candidate expression changes in the THP-1 inflammatory model.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Bone Injury, Qiannan Buyei and Miao Autonomous Prefecture Hospital of Traditional Chinese Medicine, Duyun, Guizhou, China",
    "Department of Orthopedics, The Second People’s Hospital of Kashgar Prefecture, Kashgar, Xinjiang, China",
    "Outpatient Department Physical Examination Center, General Hospital of Western Theater of Chinese People’s Liberation Army, Chengdu, Sichuan, China",
    "Department of Orthopaedics, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Guangying Tang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinjun Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yongchun Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhiyu Tang"
    },
    {
      "affs": [
        3
      ],
      "name": "He Liang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1y65azc2wxksd.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1944218",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731304/",
  "id": "1y65azc2wxksd",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1944218",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2732|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7223087856",
  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1944218/pdf",
  "pmcid": "PMC13731304",
  "pmid": "42984970",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1y65azc2wxksd.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:31Z",
      "native_id": "PMC13731304",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1944218"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2732|Spine and Intervertebral Disc Pathology",
      "subfield": "surgery"
    }
  ],
  "title": "Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing",
  "title_text": "Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:31Z",
  "url": "https://research.draconitic.com/paper/1y65azc2wxksd",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}