{
  "abstract": "The immune environment influences neurodevelopment and subsequent clinical trajectories for psychiatric outcomes in childhood and adolescence. Yet it remains unclear if the impact of maternal and fetal immune activation varies with distinct polygenic risk profiles. Therefore, here we catalog genotype and environment (GxE) interactions, contrasting allele-specific regulatory activity between inflammatory cues. We report a cue-specific neuronal massively parallel reporter assay (MPRA) of 152 loci from genome-wide association studies (GWAS) of ten brain traits/disorders, empirically dissecting the impact of interleukin-6 (IL-6) and interferon-alpha (IFNα) on transcriptional activity. In human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons, 1,156 active candidate regulatory risk sequences (MPRA-active CRSs) are resolved, including 267 with variant-specific effects (MPRA-emVars) and 61 with variant-by-cytokine interaction effects (interaction MPRA-emVars). Broadly, neuronal immune-mediated regulatory activity is associated with differences in transcription factor binding and chromatin accessibility, the gene targets of which show pleiotropic enrichments for brain, metabolic, and immune disorders. Dynamic genetic regulation mediates neuroimmune effects, informing our understanding of the genomics of psychiatric and neurological traits, mechanisms governing pleiotropy across disorders, and how immune mechanisms mediate genetic risk.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Genetics, Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA",
    "Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA. laura.huckins@yale.edu",
    "Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kristen.brennand@yale.edu",
    "Department of Genetics, Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA. kristen.brennand@yale.edu",
    "Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA. kristen.brennand@yale.edu",
    "Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kristen.brennand@yale.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kayla G. Townsley",
      "orcid": "0000-0003-4706-5752"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "S. H. Lee",
      "orcid": "0009-0007-4907-0033"
    },
    {
      "affs": [
        2
      ],
      "name": "Sarah Williams",
      "orcid": "0000-0003-3624-611X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sam Cartwright"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sophie Cohen"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Annabel Sen",
      "orcid": "0009-0003-2012-4668"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Meng Jia"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Hannah E. Young",
      "orcid": "0000-0002-4248-9612"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Lee Dobbyn"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Michael Deans"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Meilín Fernández García",
      "orcid": "0000-0002-8745-9775"
    },
    {
      "affs": [
        6
      ],
      "name": "Laura M. Huckins",
      "orcid": "0000-0002-5369-6502"
    },
    {
      "affs": [
        7,
        8,
        9,
        10
      ],
      "name": "Kristen Brennand",
      "orcid": "0000-0003-0993-5956"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/esgf04rj3fq31.bib",
  "cited_by": 14,
  "doi": "10.1038/s41467-026-77114-x",
  "fulltext_url": null,
  "id": "esgf04rj3fq31",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-77114-x",
  "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": "W7204475549",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77114-x_reference.pdf",
  "pmcid": "PMC11257632",
  "pmid": "39026810",
  "published": "2026-08-27",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/esgf04rj3fq31.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7204475549",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-77114-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Associations and Epidemiology",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Dynamic neuro-immune regulation of psychiatric risk loci in human neurons",
  "title_text": "Dynamic neuro-immune regulation of psychiatric risk loci in human neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/esgf04rj3fq31",
  "venue": "Nature Communications",
  "versions": []
}