{
  "abstract": "Gene expression varies substantially across cells, even within seemingly homogeneous populations. Understanding how genetic variation influences this variability is critical for elucidating mechanisms of genome regulation, yet the genetic control of cell-to-cell expression variability remains poorly characterised. Here, we introduce MEOTIVE (Mapping genetic Effects On inTra-Individual Variability of gene Expression), a statistical framework that identifies genetic effects on gene expression variability (sc-veQTLs) while modelling mean-variance dependence. Applying MEOTIVE to single-cell RNA-seq data from 1.2 million peripheral blood mononuclear cells across 980 donors in the OneK1K cohort, we identify 14–3,488 genes with significant sc-veQTLs across blood cell types, including 2,103 shared across multiple cell types. We further detect 55 SNP-gene pairs (34 genes) associated with gene expression dispersion (sc-deQTLs), enriched for immune and viral response pathways; 32 of these associations remain significant after additional adjustment for mean expression. Notably, rs1131017 in the 5′UTR of RPS26 is associated with widespread expression dispersion across cell types and reduced autoimmune disease risk. We also identify a monocyte-specific deQTL in LYZ (rs1384), which replicates in an independent cohort. MEOTIVE provides a robust framework for mapping the genetic regulation of gene-expression variability at single-cell resolution and reveals pathways linking cellular heterogeneity to autoimmune disease risk.",
  "abstract_shown": true,
  "affiliations": [
    "Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW Australia",
    "School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW Australia",
    "Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD Australia",
    "Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA USA",
    "Centre for Population Genomics, Garvan Institute of Medical Research, Sydney, NSW Australia",
    "University of California, San Francisco, San Francisco, CA USA",
    "Parker Institute for Cancer Immunotherapy, San Francisco, CA USA",
    "Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS Australia",
    "UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, NSW Australia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Angli Xue",
      "orcid": "0000-0002-0285-0426"
    },
    {
      "affs": [
        0
      ],
      "name": "Seyhan Yazar",
      "orcid": "0000-0003-0994-6196"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "José Alquicira-Hernández",
      "orcid": "0000-0002-9049-7780"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Anna S. E. Cuomo",
      "orcid": "0000-0001-5168-6979"
    },
    {
      "affs": [
        0
      ],
      "name": "Anne Senabouth",
      "orcid": "0000-0002-8798-9821"
    },
    {
      "affs": [
        5
      ],
      "name": "Gracie Gordon",
      "orcid": "0000-0003-4321-9187"
    },
    {
      "affs": [
        5
      ],
      "name": "Pooja Kathail"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Chun Jimmie Ye"
    },
    {
      "affs": [
        7
      ],
      "name": "Alex W. Hewitt",
      "orcid": "0000-0002-5123-5999"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Joseph E. Powell",
      "orcid": "0000-0002-5070-4124"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e55ref75y39cx.bib",
  "cited_by": 1,
  "doi": "10.1038/s41467-026-77453-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737049/",
  "id": "e55ref75y39cx",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-77453-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7213899711",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77453-9_reference.pdf",
  "pmcid": "PMC13737049",
  "pmid": "42982778",
  "published": "2026-09-21",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/e55ref75y39cx.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:21Z",
      "native_id": "PMC13737049",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-77453-9"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Associations and Epidemiology",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Genetic variants associated with cell-type-specific intra-individual gene expression variability reveal mechanisms of genome regulation",
  "title_text": "Genetic variants associated with cell-type-specific intra-individual gene expression variability reveal mechanisms of genome regulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:21Z",
  "url": "https://research.draconitic.com/paper/e55ref75y39cx",
  "venue": "Nature Communications",
  "versions": []
}