{
  "abstract": "How cellular senescence reshapes inherited regulatory effects across chromatin and transcription, and eventually contribute to non-coding risk loci of complex diseases, remains elusive. We generated single-cell multiome ATAC-RNA profiles from proliferating and replicatively senescent primary HUVECs derived from 100 genotyped donors. Alongside state-resolved eQTL and caQTL mapping, we implemented covariance-aware multivariate QTL mapping to identify chromatin accessibility-expression QTLs (caeQTLs), modeling accessibility and expression as a joint phenotype. Joint analysis recovered moderate, asymmetric and modality-distributed associations missed by single-modality scans, revealed senescence-associated regulatory programs, and prioritized candidate causal variants and effector genes at cardiovascular loci. Fine-mapping, chromatin-state annotation and heritability enrichment, together with independent SNP-to-gene algorithms, provided convergent orthogonal support. Mechanistic dissection revealed that rs2019090 modulates PDGFD expression and endothelial phenotypes through senescence-amplified, allele-specific, HMGA1-associated enhancer-promoter regulation. This study establishes senescence-resolved joint multiomic QTL mapping as a framework for narrowing the missing regulation gap in complex disease genetics.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Bioinformatics, State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medica"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "X. Yi"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "K. Liu"
    },
    {
      "name": "L. Zhao"
    },
    {
      "name": "F. Chen"
    },
    {
      "name": "Q. Jian"
    },
    {
      "name": "J. Wang"
    },
    {
      "name": "H. Lu"
    },
    {
      "name": "W. Dong"
    },
    {
      "name": "Y. Zhou"
    },
    {
      "name": "Y. Chang"
    },
    {
      "name": "X. Gu"
    },
    {
      "name": "P. C. Sham"
    },
    {
      "name": "D. Huang"
    },
    {
      "name": "M. J. Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a64v6gdfgabnt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752532",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752532v1.full",
  "id": "a64v6gdfgabnt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752532v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7213965911",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752532v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a64v6gdfgabnt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:37Z",
      "native_id": "10.64898/2026.09.17.752532",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752532v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Single-cell multiomic QTL mapping reveals state-dependent genetic regulation and associated gene during cellular senescence",
  "title_text": "Single-cell multiomic QTL mapping reveals state-dependent genetic regulation and associated gene during cellular senescence",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:37Z",
  "url": "https://research.draconitic.com/paper/a64v6gdfgabnt",
  "venue": "bioRxiv",
  "versions": []
}