{
  "abstract": "Observational studies have repeatedly linked osteoarthritis (OA) with Parkinsons disease (PD), but whether this reflects causality, shared genetic architecture, or artefactual mechanisms remains unresolved. We triangulated six layers of evidence: two population cohorts, genome-wide and local genetic architecture, bidirectional Mendelian randomization, shared-locus mapping, cell-type-specific analyses, and single-cell expression validation. In CHARLS (n = 7,587), knee OA was associated with higher PD risk (OR 1.88, 95% CI 1.24-2.84) with consistent depression-mediated attenuation ({approx}34%). In NHANES 2011-2018, the association was positive but imprecise (OR 1.94, 95% CI 0.44-8.52) and non-specific. Genetically, OA and PD were decoupled: genetic correlation was null-to-negative, no local correlation survived correction, and bidirectional MR was null across all pre-specified chains and sensitivity analyses. Conditional FDR identified 732 independent shared loci without directional bias; colocalization converged on a single robust shared region at MAPT 17q21.31 (posterior probability 0.975). Cell-type-specific and single-cell expression analyses did not support an expression-mediated pathway. The OA- PD association is therefore largely consistent with a phenotypic illusion (reproducible but proxy-sensitive and depression-mediated), with genome-wide genetic decoupling and only locus-restricted sharing at 17q21.31.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou City, Zhejiang Province, China"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. Yu"
    },
    {
      "name": "Z. Wu"
    },
    {
      "name": "H. Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "P. Tong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e5vjnsvjthyaf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.05.26362301",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.05.26362301v1.full",
  "id": "e5vjnsvjthyaf",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.05.26362301v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7212305473",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.05.26362301v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e5vjnsvjthyaf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:16Z",
      "native_id": "10.64898/2026.09.05.26362301",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.05.26362301v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Phenotypic illusion but genetic decoupling between osteoarthritis and Parkinson's disease",
  "title_text": "Phenotypic illusion but genetic decoupling between osteoarthritis and Parkinson's disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:16Z",
  "url": "https://research.draconitic.com/paper/e5vjnsvjthyaf",
  "venue": "medRxiv",
  "versions": []
}