{
  "abstract": "Schizophrenia (SCZ) is a highly heritable complex disorder influenced by coding and noncoding genetic variation. Its genetic causes, particularly those involving noncoding variation, are largely unknown. High-throughput CRISPR screens enable dissection of disease-associated loci and identification of noncoding regulatory elements and variants that modulate gene expression. We screened SCZ GWAS loci linked to genes that are also associated in whole-exome sequencing studies to identify regulatory elements and variants impacting expression of disease-relevant genes. We used CRISPRi paired with HCR-FlowFISH to epigenetically silence 333 putative regulatory elements and measure the downstream effects on gene expression of causal SCZ genes, FAM120A, SV2A, and STAG1, in iPSCs and iPSC-derived neurons (iNeurons). We identified 78 regulatory elements that significantly alter expression of a SCZ gene, including noncoding enhancers/silencers as well as promoters of genes and lncRNAs. Pooled prime editing screens interrogated noncoding variant influence on gene expression for SCZ-associated variants and uncharacterized common variants from diverse population studies. We find that a common variant in the promoter of SV2A, rs112851681:A>G (MAF = 3.56%, 1000 Genomes) enhances transcriptional activity in iPSCs and iNeurons. These findings show distinct noncoding mechanisms that map within GWAS signals, and provide a path forward for interrogating noncoding regulatory elements and variants in disease loci.",
  "abstract_shown": true,
  "affiliations": [
    "Duke"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "M. C. Hamilton"
    },
    {
      "name": "J. W. Riley"
    },
    {
      "name": "A. C. Nelson"
    },
    {
      "name": "B. Li"
    },
    {
      "name": "S. F. Dornbaum"
    },
    {
      "name": "A. Safi"
    },
    {
      "name": "X. Cui"
    },
    {
      "name": "I. R. Jones"
    },
    {
      "name": "A. A. Coley"
    },
    {
      "name": "K. T. Hagy"
    },
    {
      "name": "R. Rai"
    },
    {
      "name": "A. Barrera"
    },
    {
      "name": "A. S. Allen"
    },
    {
      "name": "Y. Shen"
    },
    {
      "name": "R. I. Sherwood"
    },
    {
      "name": "M. I. Love"
    },
    {
      "name": "P. F. Sullivan"
    },
    {
      "name": "C. A. Gersbach"
    },
    {
      "affs": [
        0
      ],
      "name": "G. E. Crawford"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/406k9qz1mcphp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.03.749158",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749158v1.full",
  "id": "406k9qz1mcphp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749158v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "2738|Schizophrenia research and treatment"
    ]
  ],
  "openalex": "W7213458063",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749158v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/406k9qz1mcphp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:50Z",
      "native_id": "10.64898/2026.09.03.749158",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749158v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Interrogation of noncoding schizophrenia risk variants using CRISPR-based functional genomics",
  "title_text": "Interrogation of noncoding schizophrenia risk variants using CRISPR-based functional genomics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:50Z",
  "url": "https://research.draconitic.com/paper/406k9qz1mcphp",
  "venue": "bioRxiv",
  "versions": []
}