{
  "abstract": "IntroductionLow bone mineral density (BMD) is associated with altered bone remodeling and osteoimmune regulation. We aimed to prioritize transcript-level signals supported across human expression cohorts and evaluate their attribution within local cis-regulatory architecture.\n\nMaterials and MethodsNominal differential-expression signals from GSE56815 were restricted with a predefined 25-term MSigDB thematic library. Features measurable in GSE56815 and GSE2208 underwent linear SVM ranking, LASSO, and XGBoost selection, followed by cross-cohort transcriptomic assessment. OCEL1 was examined in a four-exposure locus-aware CisMRBEEX model with NR2F6, MRPL34, BABAM1, eQTLGen cis-eQTLs, heel eBMD GWAS statistics, and UKBB337K LD.\n\nResultsThe expression screen identified 2,568 genes at nominal P<0.05; thematic restriction retained 190 candidates and 107 common features entered machine learning. Linear SVM, LASSO, and XGBoost retained 24, 18, and 9 genes and converged on CPNE1, EZR, and OCEL1. Only OCEL1 showed concordant expression direction with P<0.05 in both cohorts. In the primary 268-variant four-exposure model, OCEL1 was positively associated with heel eBMD ({beta}=0.010293, SE=0.004107, 95% CI 0.002244-0.018342, P=0.01220, PIP=0.4001; conditional coefficient on the standardized analysis scale); BABAM1 retained an oppositely directed component. The no-palindromic reconstruction remained positive with wider uncertainty ({beta}=0.007652, P=0.06739).\n\nConclusionConvergent transcriptomic evidence prioritized OCEL1, whose conditional genetic-expression component was positively associated with heel eBMD after local shared cis regulation was modeled.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing Jiaotong University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. Yao"
    },
    {
      "name": "Q. Zhong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e414sb49cm02h.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.26363200",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1.full",
  "id": "e414sb49cm02h",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1",
  "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",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "2732|Bone health and osteoporosis research"
    ]
  ],
  "openalex": "W7213747692",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e414sb49cm02h.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:56Z",
      "native_id": "10.64898/2026.09.16.26363200",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Transcriptomic and Machine-Learning Prioritization of OCEL1 in Low Bone Mineral Density With Multivariable cis-MR",
  "title_text": "Transcriptomic and Machine-Learning Prioritization of OCEL1 in Low Bone Mineral Density With Multivariable cis-MR",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:56Z",
  "url": "https://research.draconitic.com/paper/e414sb49cm02h",
  "venue": "medRxiv",
  "versions": []
}