{
  "abstract": "Colorectal cancer (CRC) disproportionately affects Hispanic individuals, who remain underrepresented in genomic discovery and lack ancestry-matched functional resources. Many CRC risk variants are non-coding, and those in 3' untranslated regions (3' UTRs) can alter microRNA (miRNA) binding sites and reprogram post-transcriptional gene regulation. Here, we identify allele-specific miRNA-binding variants at CRC risk loci within the Hispanic population using a discovery pipeline anchored to Hispanic-relevant resources. CRC-associated 3' UTR variants were compiled from the GWAS Catalog, further verified in Hispanic/Latino individuals using the All of Us Research Program cohort (n = 453), expanded into proxy sets using Admixed American-specific linkage disequilibrium, annotated against Ensembl transcripts, and evaluated with TargetScan and RNAhybrid. Screening of 38 CRC-associated 3' UTR SNPs identified 19 variants that alter miRNA binding across nine genes, with each gene represented by a variant confirmed in the Hispanic cohort. Three oncogenic loci, DCBLD2 (lead SNP rs11552978), GREM1 (lead SNP rs10318), and SMC1B (rs3747239, prioritized as an AMR-specific proxy in near-complete LD with confirmed lead rs6007600), met all prioritization criteria. In each case, the risk allele disrupts a strong miRNA-binding site, while the gene shows increased tumor expression, weak correlation between expression and methylation, and an absence of local active transcriptional chromatin marks (cCREs/H3K27Ac). These results suggest that the variants promote gene overexpression through loss of miRNA-mediated repression rather than changes in promoter methylation. Overall, the study identifies non-coding CRC susceptibility variants in the Hispanic population and highlights DCBLD2, GREM1, and SMC1B as strong candidates for functional validation.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Texas at El Paso"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "S. S. Ahmad"
    },
    {
      "name": "M. Z. I. Khan"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Roy"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6akd5cy67vc3s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.26363169",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363169v1.full",
  "id": "6akd5cy67vc3s",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363169v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7213785680",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363169v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6akd5cy67vc3s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:58Z",
      "native_id": "10.64898/2026.09.16.26363169",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.16.26363169v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Allele-Specific MicroRNA-Binding Variants at Colorectal Cancer Risk Loci in a Hispanic/Latino Population: An Integrative GWAS, All of Us, and Epigenomic Analysis",
  "title_text": "Allele-Specific MicroRNA-Binding Variants at Colorectal Cancer Risk Loci in a Hispanic/Latino Population: An Integrative GWAS, All of Us, and Epigenomic Analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:58Z",
  "url": "https://research.draconitic.com/paper/6akd5cy67vc3s",
  "venue": "medRxiv",
  "versions": []
}