{
  "abstract": "Sex-specific genetic effects on platelet aggregation may contribute to differences in thrombotic risk between women and men, yet the underlying genetic mechanisms remain poorly defined. We performed whole-genome sequencing-based genome-wide association studies (GWAS) of 19 harmonized platelet aggregation phenotypes in response to adenosine diphosphate (ADP), epinephrine (EPI), and collagen across three independent cohorts: GeneSTAR, the Framingham Heart Study (FHS) and the Old Order Amish (AMISH). Our meta-GWAS identified a cluster of low-frequency variants within a 20 kb region on chromosome 10 showing strong sex-specific associations with platelet aggregation in response to low-dose EPI. The lead variant, rs116725046, exhibited a genome-wide significant sex interaction (p = 6.7 x 10-9), with opposite phenotypic effects in women and men. Female carriers demonstrated increased platelet aggregation, whereas male carriers showed decreased aggregation, consistent across cohorts. Several variants in tight linkage disequilibrium with the lead variant yielded additional significant interaction signals for low-dose EPI. The associated variants reside within an intronic region of the long noncoding gene LINC00702, with FUMA annotations indicating regulatory chromatin states. Megakaryocyte epigenome data also indicates potential regulatory activity in platelet precursor cells in this genomic region. eQTL analyses suggested sex-differentiated genetic regulation of LINC00702 in multiple tissues, with reduced expression in male heterozygotes only. An Androgen Response Element motif was identified upstream of LINC00702, supporting a potential hormone-responsive regulatory mechanism. Together, these findings identify a novel sex-specific regulatory locus associated with platelet reactivity and highlight LINC00702 as a biologically plausible mediator of sexually dimorphic platelet responses.",
  "abstract_shown": true,
  "affiliations": [
    "Johns Hopkins University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "J. S. Ngwa"
    },
    {
      "name": "M.-H. Chen"
    },
    {
      "name": "G. Brady"
    },
    {
      "name": "L. R. Yanek"
    },
    {
      "name": "K. Kammers"
    },
    {
      "name": "K. Kanchan"
    },
    {
      "name": "M. A. Taub"
    },
    {
      "name": "Y. Dun"
    },
    {
      "name": "N. Chatterjee"
    },
    {
      "name": "K. A. Ryan"
    },
    {
      "name": "NHLBI Trans-Omics for Precision (TOPMed) Consortium"
    },
    {
      "name": "L. C. Becker"
    },
    {
      "name": "R. A. Mathias"
    },
    {
      "name": "J. P. Lewis"
    },
    {
      "name": "A. D. Johnson"
    },
    {
      "name": "N. Faraday"
    },
    {
      "affs": [
        0
      ],
      "name": "I. Ruczinski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c9w6bqgr1e4m3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.14.26353192",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.05.14.26353192v2.full",
  "id": "c9w6bqgr1e4m3",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.05.14.26353192v2",
  "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",
      "2720|Platelet Disorders and Treatments"
    ]
  ],
  "openalex": "W7161563992",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.05.14.26353192v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c9w6bqgr1e4m3.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:20:55Z",
      "native_id": "10.64898/2026.05.14.26353192",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.05.14.26353192v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "A genome-wide meta-analysis identifies a sex-specific genetic effect for platelet aggregation in response to agonists",
  "title_text": "A genome-wide meta-analysis identifies a sex-specific genetic effect for platelet aggregation in response to agonists",
  "type": "preprint",
  "updated_at": "2026-11-08T00:20:57Z",
  "url": "https://research.draconitic.com/paper/c9w6bqgr1e4m3",
  "venue": "medRxiv",
  "versions": []
}