{
  "abstract": "Observational studies link matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) to ankylosing spondylitis (AS), but causality is uncertain. We performed a bidirectional, 2-sample Mendelian randomization (MR) analysis using genetic variants to assess causal relationships between genetically predicted circulating levels of 14 MMPs and 4 TIMPs and AS risk, and to evaluate reverse causation. Genetic instruments for circulating MMPs and TIMPs were derived from a large proteogenomic genome-wide association study of 5368 individuals. Summary statistics for AS were obtained from the FinnGen Release 12 GWAS (3838 cases; 353,224 controls). Causal estimates were generated using inverse-variance weighting (primary analysis), complemented by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses included Cochran’s Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses. Forward MR identified a nominal association between genetically predicted higher circulating MMP13 levels and an increased risk of AS (IVW odds ratio = 1.223, 95% confidence interval, 1.048–1.428; P = .011, FDR = 0.198). This association showed a consistent direction in the weighted median estimates and showed no evidence of heterogeneity or horizontal pleiotropy. No other MMPs or TIMPs showed convincing evidence of an association with AS. Reverse MR analyses provided no evidence that genetic liability to AS causally influences circulating MMP or TIMP levels. This bidirectional MR analysis provides genetic support for a potential causal relationship between MMP13 and the development of AS, while suggesting that other MMPs and TIMPs are unlikely to be causal drivers. Further experimental and clinical studies are warranted to clarify the biological relevance of MMP13 in AS.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Ningbo No 6 Hospital, Ningbo, Zhejiang, China",
    "Ningbo Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Ningbo, Zhejiang, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoyang Sun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Guoqing Li",
      "orcid": "0000-0002-2712-691X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Huaguo Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yang Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b44tedb4k83k5.bib",
  "cited_by": 0,
  "doi": "10.1097/md.0000000000051374",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727261/?tool=EBI",
  "id": "b44tedb4k83k5",
  "issns": [
    "0304-5412",
    "1536-5964",
    "0025-7974"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13727261",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "6900"
    ],
    [
      "heading",
      "Observational Study"
    ],
    [
      "heading",
      "Research Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727261/pdf/?tool=EBI",
  "pmcid": "PMC13727261",
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Wolters Kluwer Health",
  "ris": "https://research.draconitic.com/paper/b44tedb4k83k5.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13727261",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727261"
    },
    {
      "first_seen": "2026-11-05T12:23:22Z",
      "native_id": "PMC13727261",
      "source": "pmc",
      "url": "https://doi.org/10.1097/md.0000000000051374"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Association of 14 matrix metalloproteinases and 4 tissue inhibitors of metalloproteinases on ankylosing spondylitis : A bidirectional Mendelian randomization study",
  "title_text": "Association of 14 matrix metalloproteinases and 4 tissue inhibitors of metalloproteinases on ankylosing spondylitis : A bidirectional Mendelian randomization study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:23:22Z",
  "url": "https://research.draconitic.com/paper/b44tedb4k83k5",
  "venue": "Medicine",
  "versions": []
}