{
  "abstract": "Here, we conduct a large meta-analysis of DNA methylation across multiple cortical brain regions, in relation to increasing burden of Lewy body pathology. Utilizing a dataset of 1205 samples (832 unique donors), we identify 24 false discovery rate significant differentially methylated loci associated with Lewy body pathology, with loci located in UBASH3B and PTAFR, and an intergenic locus passing the genome-wide significance threshold. Ontological enrichment analysis highlights several neurologically relevant traits, including synaptic alterations. We compare methylation signatures between neurodegenerative pathologies and highlight a shared epigenetic profile across Lewy body, Alzheimer's and Huntington's diseases, although the top-ranked loci show disease specificity. Utilizing summary statistics from large-scale genome-wide association studies, we identify significant enrichment of DNA methylation differences with respect to increasing Lewy body pathology in the SNCA genomic region. We also identify specific relationships between genetic risk variants for Lewy body dementia and Parkinson's disease to methylation quantitative trait loci in the SNCA 5' region and expression of alternative transcript isoforms.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.",
    "Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University of London, London, UK.",
    "Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.",
    "Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.",
    "Specialty Dementia and Frailty Service, Essex Partnership University NHS Foundation Trust, St Margaret's Hospital, Epping, UK.",
    "Great Ormond Street Hospital, University College London, London, UK.",
    "Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, University College London, London, UK.",
    "Newcastle Brain Tissue Resource, Newcastle University, Newcastle, UK.",
    "MS and Parkinson's Tissue Bank, Department of Brain Sciences, Imperial College London, London, UK.",
    "The Oxford Brain Bank, University of Oxford, Oxford, UK.",
    "Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.",
    "Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.",
    "Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Kings College London, London, UK.",
    "Institute of Clinical Medicine, University of Oslo, Oslo, Norway.",
    "Department of Neurology, Oslo University Hospital, Oslo, Norway.",
    "Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK. k.lunnon@exeter.ac.uk."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Joshua Harvey",
      "orcid": "0000-0001-6423-9983"
    },
    {
      "affs": [
        0
      ],
      "name": "Jennifer Imm"
    },
    {
      "affs": [
        0
      ],
      "name": "Morteza Kouhsar",
      "orcid": "0000-0001-6092-3016"
    },
    {
      "affs": [
        0
      ],
      "name": "Adam R Smith",
      "orcid": "0000-0001-6495-2711"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Byron Creese"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebecca G Smith",
      "orcid": "0000-0001-9264-1056"
    },
    {
      "affs": [
        0
      ],
      "name": "Gregory Wheildon"
    },
    {
      "affs": [
        2
      ],
      "name": "Valentin Laroche"
    },
    {
      "affs": [
        0
      ],
      "name": "Szi Kay Leung",
      "orcid": "0000-0002-5607-4688"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Leonidas Chouliaras"
    },
    {
      "affs": [
        5
      ],
      "name": "Gemma Shireby"
    },
    {
      "affs": [
        6
      ],
      "name": "Zane Jaunmuktane",
      "orcid": "0000-0001-7738-8881"
    },
    {
      "affs": [
        6
      ],
      "name": "Eduardo De Pablo-Fernández"
    },
    {
      "affs": [
        6
      ],
      "name": "Thomas Warner",
      "orcid": "0000-0001-6195-6995"
    },
    {
      "affs": [
        7
      ],
      "name": "Debra J Lett"
    },
    {
      "affs": [
        8
      ],
      "name": "Djordje Gveric"
    },
    {
      "affs": [
        9
      ],
      "name": "Hannah Brooks"
    },
    {
      "affs": [
        7
      ],
      "name": "Johannes Attems"
    },
    {
      "affs": [
        7
      ],
      "name": "Alan Thomas"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Wilma Dj Van de Berg",
      "orcid": "0000-0002-6175-5357"
    },
    {
      "affs": [
        0
      ],
      "name": "Emma Dempster",
      "orcid": "0000-0003-1257-5314"
    },
    {
      "affs": [
        0
      ],
      "name": "Clive Ballard",
      "orcid": "0000-0003-0022-5632"
    },
    {
      "affs": [
        3
      ],
      "name": "John T O'Brien",
      "orcid": "0000-0002-0837-5080"
    },
    {
      "affs": [
        12
      ],
      "name": "Dag Aarsland",
      "orcid": "0000-0001-6314-216X"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonathan Mill"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Lasse Pihlstrøm",
      "orcid": "0000-0002-7635-8645"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ehsan Pishva",
      "orcid": "0000-0002-8964-0682"
    },
    {
      "affs": [
        15
      ],
      "name": "Katie Lunnon",
      "orcid": "0000-0001-7570-6065"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c134d64nc6941.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77009-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13672336",
  "id": "c134d64nc6941",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42881165",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7213290215",
  "pdf_url": "https://europepmc.org/articles/PMC13672336?pdf=render",
  "pmcid": "PMC13672336",
  "pmid": "42881165",
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c134d64nc6941.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42881165",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42881165"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.",
  "title_text": "Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/c134d64nc6941",
  "venue": "Nature communications",
  "versions": []
}