{
  "abstract": "Multiple sclerosis (MS) is approximately three times more common in females than in males, but sex-linked epigenetic mechanisms remain incompletely understood. We tested whether X-chromosome DNA methylation differs in females with MS and whether associated sites preferentially map to genes normally subject to X-chromosome inactivation (XCI). An X-chromosome-focused epigenome-wide association study was performed in whole blood from three datasets comprising 496 females with MS and 509 female controls, with independent evaluation in isolated CD4+ T cells (80 cases, 76 controls). At FDR < 0.01, 3 182 X-chromosome CpGs were hypomethylated in MS (mean {Delta}{beta} = -0.035). Hypomethylated CpGs were strongly enriched in non-escape genes normally subject to XCI relative to escape genes (OR 6.77; p = 1.55x10) and mapped to immune and chromatin-related processes. Exploratory cis-mQTL analysis identified strong local genetic effects at a small subset of loci, including WAS, IRAK1 and TLR7. In CD4+ T cells, 2 080 of the 3 182 whole-blood hypomethylated CpGs (65.4%) were also significantly hypomethylated. These findings identify a reproducible X-chromosome hypomethylation signature in female MS and support direct investigation of inactive-X regulation, XCI escape and X-linked immune gene dosage.",
  "abstract_shown": true,
  "affiliations": [
    "Hunter Medical Research Institute"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "T. Calnin"
    },
    {
      "name": "V. E. Maltby"
    },
    {
      "name": "S. M. Burnard"
    },
    {
      "name": "A. Xavier"
    },
    {
      "name": "S. Simpson-Yap"
    },
    {
      "name": "I. van der Mei"
    },
    {
      "name": "S. Broadley"
    },
    {
      "name": "B. V. Taylor"
    },
    {
      "name": "H. Butzkueven"
    },
    {
      "name": "A.-L. Ponsonby"
    },
    {
      "name": "R. J. Scott"
    },
    {
      "name": "M. Jagodic"
    },
    {
      "name": "V. G. Jokubaitis"
    },
    {
      "name": "J. Lechner-Scott"
    },
    {
      "affs": [
        0
      ],
      "name": "R. A. Lea"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9kz9qzsn7jsmr.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.13.26365261",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365261v1.full",
  "id": "9kz9qzsn7jsmr",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365261v1",
  "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",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7221749979",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365261v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9kz9qzsn7jsmr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:50Z",
      "native_id": "10.64898/2026.10.13.26365261",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365261v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "X-chromosome methylation patterns in females with multiple sclerosis",
  "title_text": "X-chromosome methylation patterns in females with multiple sclerosis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:50Z",
  "url": "https://research.draconitic.com/paper/9kz9qzsn7jsmr",
  "venue": "medRxiv",
  "versions": []
}