{
  "abstract": "The All of Us (AoU) Research Program multi-omics cohort was developed to expand discovery of the molecular mechanisms underlying health and disease. Here, we report on the AoU multi-omics cohort comprising proteomic (N = 10,043) and transcriptomic (N = 9,043) sequencing data generated from ancestrally diverse AoU participants. We provide comprehensive expression, splicing, and protein quantitative trait locus (e/s/pQTL) analyses and detected 182,246 QTLs, of which 54,255 finemapped to rare variants and 59.4% (32,235) resolve to a single causal variant. We provide multiple insights into rare variant effects and demonstrate that they are more likely to be ancestrally-restricted, replicate across molecular layers and impact known Mendelian disease genes (OR = 1.4) and approved drug targets (OR = 1.3). Rare variant QTLs from AoU further provided evidence for 5,186 variants, many absent from ClinVar, affecting established disease genes. Combined, the availability of multi-omics in AoU provides a key resource to identify the genetic and molecular mechanisms impacting health and disease across multiple ancestry groups in the United States.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA; Department of Biomedical Data S"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "E. M. Padhi"
    },
    {
      "name": "E. A. Kiernan"
    },
    {
      "name": "J. V. Nguyen"
    },
    {
      "name": "M. K. DeGorter"
    },
    {
      "name": "V. S. Rosa"
    },
    {
      "name": "Y. Mostovoy"
    },
    {
      "name": "A. L. Yenkin"
    },
    {
      "name": "H. Su"
    },
    {
      "name": "L. Lichtenstein"
    },
    {
      "name": "A. R. Marderstein"
    },
    {
      "name": "J. Gillard"
    },
    {
      "name": "W. Baalawi"
    },
    {
      "name": "S. J. Parsa"
    },
    {
      "name": "M. S. Cicek"
    },
    {
      "name": "J. G. Meyer"
    },
    {
      "name": "A. L. Blegen"
    },
    {
      "name": "V. A. McNally"
    },
    {
      "name": "J. J. Lane"
    },
    {
      "name": "Z. S. Fredericksen"
    },
    {
      "name": "All of Us Research Program Multi-omics Working Group"
    },
    {
      "name": "The All of Us Research Program"
    },
    {
      "name": "N. Gupta"
    },
    {
      "name": "H. Brand"
    },
    {
      "name": "K. Garimella"
    },
    {
      "name": "K. J. Karczewski"
    },
    {
      "name": "M. E. Talkowski"
    },
    {
      "name": "N. J. Lennon"
    },
    {
      "affs": [
        0
      ],
      "name": "S. B. Montgomery"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/85ssqm7q2b654.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.29.26366507",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.29.26366507v1.full",
  "id": "85ssqm7q2b654",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.29.26366507v1",
  "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": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7225040256",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.29.26366507v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/85ssqm7q2b654.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:20:44Z",
      "native_id": "10.64898/2026.10.29.26366507",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.29.26366507v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Multi-omics in the All Of Us Research Program expands mapping genetic mechanisms in health and disease",
  "title_text": "Multi-omics in the All Of Us Research Program expands mapping genetic mechanisms in health and disease",
  "type": "preprint",
  "updated_at": "2026-11-03T00:20:22Z",
  "url": "https://research.draconitic.com/paper/85ssqm7q2b654",
  "venue": "medRxiv",
  "versions": []
}