{
  "abstract": "Common brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging 1 . Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many of these loci lie in non-coding regions that influence gene expression in specific cell types 2–5 . Traditional bulk brain transcriptomic analyses, which often focus on European ancestry cohorts, average over cellular diversity, obscuring genetic risk-related changes in gene expression. Here we use single-nucleus gene expression profiles from the dorsolateral prefrontal cortex in the multi-ancestry PsychAD cohort to develop transcriptomic imputation models of genetically regulated expression across major brain cell types. Applying these models to neuropsychiatric and neurodegenerative disorders reveals thousands of gene–trait associations that are undetectable in bulk tissue analyses and resolves many signals to discrete neuronal, glial and immune cell populations. Cross-ancestry analyses in the Million Veteran Program confirm these associations, reveal pleiotropic effects of cell-type-specific predicted expression and demonstrate that trait-related dysregulation is conserved across ancestries, enabling mapping of causal genes and pathways. Together, these findings provide a cell-type-resolved and ancestry-aware atlas of genetically regulated expression in the human prefrontal cortex and illustrate how single-nucleus transcriptomics can sharpen gene discovery and therapeutic target prioritization for complex brain disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY, USA",
    "Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, NY, USA",
    "Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA",
    "Institute for Genomics in Health (IGH), SUNY Downstate Health Sciences University, Brooklyn, NY, USA",
    "Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USA",
    "Waisman Center, University of Wisconsin-Madison, Madison, WI, USA",
    "Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA",
    "Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark",
    "Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA",
    "Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA",
    "Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institutes, San Francisco, CA, USA",
    "Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA",
    "Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA",
    "Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA",
    "Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Center for Systems and Therapeutics, Gladstone Institutes, San Francisco, CA, USA",
    "Human Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA",
    "Department of Neurology, University of California San Francisco, San Francisco, CA, USA",
    "Department of Physiology, University of California San Francisco, San Francisco, CA, USA",
    "Neuroscience and Biomedical Sciences Graduate Programs, University of California San Francisco, San Francisco, CA, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 78,
  "authors": [
    {
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      ],
      "name": "Sanan Venkatesh",
      "orcid": "0000-0002-3094-2731"
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      "name": "Roman Kosoy",
      "orcid": "0000-0002-3080-7900"
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        4
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      "name": "Zhenyi Wu",
      "orcid": "0009-0001-4180-7877"
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        4
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      "name": "Marios Anyfantakis",
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      "name": "Christian Dillard",
      "orcid": "0000-0001-5740-7328"
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      "name": "N. M. Prashant",
      "orcid": "0000-0003-3548-5637"
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      "name": "David Burstein"
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      "name": "Deepika Dayal Mathur",
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      "name": "Chris Chatzinakos"
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      "name": "Biao Zeng"
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      "name": "Sonali Gupta",
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      "name": "Rachel Bercovitch",
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      "name": "Aram Hong",
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      "name": "Stathis Argyriou",
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      "name": "Chenfeng He"
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      "name": "Chirag Gupta",
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      "name": "Collin Spencer"
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      "name": "Daifeng Wang",
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      "name": "Fotis Tsetsos",
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      "name": "Gennadi Ryan",
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      "name": "Hui Yang",
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      "name": "Jaroslav Bendl"
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      "name": "Jennifer Monteiro Fortes",
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      "name": "Jerome J. Choi",
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      "name": "Kalpana Hanthanan Arachchilage",
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      "name": "Logan C. Dumitrescu",
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      "name": "Madeline R. Scott",
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      "name": "Marios Anyfantakis",
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      "name": "Maxim Signaevsky",
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      "name": "Milos Pjanic",
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      "name": "Monika Ahirwar",
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      "name": "Nicolas Y. Masse",
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      "name": "Noah Cohen Kalafut",
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      "name": "Pavan Kumar Auluck",
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      "name": "Pavel Katsel",
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      "name": "Pramod B. Chandrashekar"
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      "name": "Sanan Venkatesh",
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      "name": "Saniya Khullar",
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      "name": "Seon Kinrot",
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      "orcid": "0000-0002-9213-9629"
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      ],
      "name": "Tereza Clarence",
      "orcid": "0000-0002-0099-2797"
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      "name": "Timothy J. Hohman",
      "orcid": "0000-0002-3377-7014"
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  ],
  "bibtex": "https://research.draconitic.com/paper/92vkg180jgtqj.bib",
  "cited_by": 7,
  "doi": "10.1038/s41586-026-10836-6",
  "fulltext_url": null,
  "id": "92vkg180jgtqj",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10836-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "1312|Single-cell and spatial transcriptomics"
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  "pdf_url": "https://www.nature.com/articles/s41586-026-10836-6.pdf",
  "pmcid": "PMC13600940",
  "pmid": "42778697",
  "published": "2026-09-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/92vkg180jgtqj.ris",
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      "first_seen": "2026-10-30T13:26:48Z",
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      "url": "https://doi.org/10.1038/s41586-026-10836-6"
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  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Single-nucleus transcriptome-wide association study of human brain disorders",
  "title_text": "Single-nucleus transcriptome-wide association study of human brain disorders",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T13:20:30Z",
  "url": "https://research.draconitic.com/paper/92vkg180jgtqj",
  "venue": "Nature",
  "versions": []
}