{
  "abstract": "Understanding the genetic basis of gene expression can shed light on the regulatory mechanisms underlying complex traits and diseases. Single cell-resolved measures of RNA levels and single-cell expression quantitative trait loci (sc-eQTLs) have revealed genetic regulation that drives sub-tissue cell states and types across diverse human tissues. Here, we describe the first phase of TenK10K, the largest-to-date dataset of matched whole-genome sequencing (WGS) and single-cell RNA-sequencing (scRNA-seq). We leverage scRNA-seq data from over 5 million cells across 28 immune cell types, and matched WGS, from 1,925 individuals, which provides power to detect associations between rare and low-frequency genetic variants that have largely been uncharacterised in their impact on cell-specific gene expression. We map the effects of both common and rare variants in a cell type-specific manner using a recently introduced method that increases power by modelling single cells directly rather than relying on aggregated ‘pseudobulk’ counts. We identify putative common regulatory variants for 83% of all 21,404 genes tested and cumulative rare variant signals for 47% of genes. We explore how genetic effects vary across cell type and state spectra, develop a framework to determine the degree to which sc-eQTLs are cell type-specific, and show that about half of the effects are observed only in one or a few cell types. By integrating our results with functional annotations and disease information, we also further characterise the likely molecular modes of action for many disease-variant associations. Finally, we explore the effects that genetic variants have on gene expression across continuous cell states and functions, and effects that vary cell state abundance directly.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Population Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia",
    "Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia",
    "Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia",
    "Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia",
    "UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, New South Wales, Australia",
    "Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia",
    "Institute of Cardiovascular Science, University College London, London, UK",
    "Faculty of Science, University of Sydney, Sydney, New South Wales, Australia",
    "Massachusetts General Hospital, Boston, MA, USA",
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "MRC Biostatistics Unit, University of Cambridge, Cambridge, UK",
    "Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia",
    "Department of Ophthalmology, Royal Hobart Hospital, Hobart, Tasmania, Australia",
    "Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia",
    "Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia",
    "Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia",
    "Genomics and Inherited Diseases Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia",
    "Illumina Artificial Intelligence Laboratory, Illumina, San Diego, CA, USA",
    "Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK",
    "Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. j.powell@garvan.org.au",
    "Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. j.powell@garvan.org.au",
    "UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, New South Wales, Australia. j.powell@garvan.org.au"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 44,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Anna S. E. Cuomo",
      "orcid": "0000-0001-5168-6979"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Eleanor Spenceley",
      "orcid": "0009-0000-5543-2810"
    },
    {
      "affs": [
        0,
        1,
        2,
        5
      ],
      "name": "Hope A. Tanudisastro",
      "orcid": "0000-0002-4561-305X"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Blake Bowen"
    },
    {
      "affs": [
        2,
        3,
        6,
        4
      ],
      "name": "Albert Henry",
      "orcid": "0000-0001-7422-2288"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Hao Lawrence Huang",
      "orcid": "0000-0001-8960-8941"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Angli Xue",
      "orcid": "0000-0002-0285-0426"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Wei Zhou",
      "orcid": "0000-0001-7719-0859"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Matthew J. Welland",
      "orcid": "0000-0001-5963-863X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Samantha J. Bryen",
      "orcid": "0000-0002-4140-8622"
    },
    {
      "affs": [
        7,
        3
      ],
      "name": "Oscar A Dong",
      "orcid": "0009-0009-8275-2989"
    },
    {
      "affs": [
        9,
        8
      ],
      "name": "Arthur S. Lee",
      "orcid": "0000-0002-4513-4630"
    },
    {
      "affs": [
        10
      ],
      "name": "Jeffrey M. Pullin",
      "orcid": "0000-0003-3651-5471"
    },
    {
      "affs": [
        11,
        12,
        13
      ],
      "name": "Kristof Wing",
      "orcid": "0000-0002-7136-9484"
    },
    {
      "affs": [
        14,
        5,
        15
      ],
      "name": "Owen Tang",
      "orcid": "0000-0001-5878-1311"
    },
    {
      "affs": [
        14,
        5,
        15
      ],
      "name": "Michael Patrick Gray",
      "orcid": "0000-0003-1154-3011"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael Franklin",
      "orcid": "0000-0001-9292-1533"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael Harper"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael A. Silk",
      "orcid": "0000-0001-5855-8750"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Katalina Bobowik",
      "orcid": "0000-0002-7030-3969"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alexander Stuckey",
      "orcid": "0000-0001-8636-737X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "John Marshall",
      "orcid": "0000-0002-1216-5457"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Vivian Bakiris"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Caitlin Uren",
      "orcid": "0000-0003-2358-0135"
    },
    {
      "affs": [
        3
      ],
      "name": "Rachael A. McCloy",
      "orcid": "0000-0001-7791-4044"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bindu Swapna Madala",
      "orcid": "0000-0001-6090-6638"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Amy Miniter",
      "orcid": "0000-0003-2084-9477"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Caitlin Bartie"
    },
    {
      "affs": [
        3
      ],
      "name": "Drew R. Neavin",
      "orcid": "0000-0002-1783-6491"
    },
    {
      "affs": [
        2,
        16
      ],
      "name": "Zhen Qiao"
    },
    {
      "affs": [
        17
      ],
      "name": "Eyal David",
      "orcid": "0000-0002-9020-2364"
    },
    {
      "affs": [
        17
      ],
      "name": "Ling Chen",
      "orcid": "0009-0005-1326-4069"
    },
    {
      "affs": [
        17
      ],
      "name": "Kyle Kai‐How Farh",
      "orcid": "0000-0001-6947-8537"
    },
    {
      "affs": [
        14
      ],
      "name": "Stuart M. Grieve",
      "orcid": "0000-0002-2712-157X"
    },
    {
      "affs": [
        14,
        5,
        15
      ],
      "name": "Trinh Xuan Nguyen",
      "orcid": "0000-0003-1294-7739"
    },
    {
      "affs": [
        18,
        10
      ],
      "name": "Chris Wallace"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jennifer Piscionere",
      "orcid": "0000-0002-1091-8734"
    },
    {
      "affs": [
        2,
        16
      ],
      "name": "Owen M. Siggs",
      "orcid": "0000-0003-2840-4851"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hannah Nicholas"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Katrina M. de Lange"
    },
    {
      "affs": [
        11,
        12,
        13
      ],
      "name": "Alex William Hewitt",
      "orcid": "0000-0002-5123-5999"
    },
    {
      "affs": [
        14,
        5,
        15
      ],
      "name": "Gemma A. Figtree"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Daniel G. MacArthur",
      "orcid": "0000-0002-5771-2290"
    },
    {
      "affs": [
        19,
        20,
        21
      ],
      "name": "Joseph E. Powell",
      "orcid": "0000-0002-5070-4124"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bt6bg4jzf82k4.bib",
  "cited_by": 33,
  "doi": "10.1038/s41586-026-10721-2",
  "fulltext_url": null,
  "id": "bt6bg4jzf82k4",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10721-2",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W4408741192",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42951973",
  "published": "2026-10-28",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/bt6bg4jzf82k4.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T13:20:37Z",
      "native_id": "W4408741192",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10721-2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Associations and Epidemiology",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Rare and common genetic variants shape single-cell immune gene expression",
  "title_text": "Rare and common genetic variants shape single-cell immune gene expression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/bt6bg4jzf82k4",
  "venue": "Nature",
  "versions": []
}