{
  "abstract": "Sex differences exist in complex diseases, but the genetic architecture of sex differences in quantitative clinical traits is understudied. Here, we performed sex-stratified genome-wide association studies of 508 clinical traits from electronic health records (EHRs) in 64,956 European-ancestry individuals in the Vanderbilt biobank, BioVU, with replication in the UK Biobank and Colorado Center for Personalized Medicine biobank. Most trait distributions differed significantly by sex. We identified a female-specific locus for erythrocyte distribution width at PIEZO1 and sex-differentiated effect magnitudes at APOE (LDL cholesterol) and SLC2AS (uric acid) that replicated across biobanks, varied with age, and partially mediated associations with heart disease and gout. Opposite-direction sex effects were less replicable. Ascertainment bias could be addressed using inverse-probability weighting. Sex-stratified colocalization with eOTLs nominated additional candidate genes. Differential effect magnitude, not opposing effects, predominate in sex- specific genetic architecture, requiring large sample sizes for discovery that can be achieved using EHR data.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "F. A. Blostein"
    },
    {
      "name": "B. Bose"
    },
    {
      "name": "A. Hill"
    },
    {
      "name": "K. Actkins"
    },
    {
      "name": "A. M. Lake"
    },
    {
      "name": "N. Freilich"
    },
    {
      "name": "P. Straub"
    },
    {
      "name": "M. Niarchou"
    },
    {
      "name": "B. E. Stranger"
    },
    {
      "name": "L. K. Davis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/48q16125qsthj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.02.26362069",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.02.26362069v1.full",
  "id": "48q16125qsthj",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.02.26362069v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7211968756",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.02.26362069v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/48q16125qsthj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "10.64898/2026.09.02.26362069",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.02.26362069v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Sex differences in the genetic architecture of clinical quantitative traits in the electronic health record",
  "title_text": "Sex differences in the genetic architecture of clinical quantitative traits in the electronic health record",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/48q16125qsthj",
  "venue": "medRxiv",
  "versions": []
}