Evidence map›Paper›PMID 42881165›Full record

SynthesisNature communications2026

Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.

Joshua Harvey, Jennifer Imm, Morteza Kouhsar, Adam R Smith, Byron Creese, Rebecca G Smith, Gregory Wheildon, Valentin Laroche, Szi Kay Leung, Leonidas Chouliaras and 18 more

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Joshua Harvey *Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0001-6423-9983
Jennifer Imm *Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Morteza KouhsarDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0001-6092-3016
Adam R SmithDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0001-6495-2711
Byron CreeseDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Rebecca G SmithDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0001-9264-1056
Gregory WheildonDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Valentin LarocheDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.
Szi Kay LeungDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0002-5607-4688
Leonidas ChouliarasDepartment of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Gemma ShirebyGreat Ormond Street Hospital, University College London, London, UK.
Zane JaunmuktaneQueen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-7738-8881
Eduardo De Pablo-FernándezQueen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, University College London, London, UK.
Thomas WarnerQueen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-6195-6995
Debra J LettNewcastle Brain Tissue Resource, Newcastle University, Newcastle, UK.
Djordje GvericMS and Parkinson's Tissue Bank, Department of Brain Sciences, Imperial College London, London, UK.
Hannah BrooksThe Oxford Brain Bank, University of Oxford, Oxford, UK.
Johannes AttemsNewcastle Brain Tissue Resource, Newcastle University, Newcastle, UK.
Alan ThomasNewcastle Brain Tissue Resource, Newcastle University, Newcastle, UK.
Wilma Dj Van de BergDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-6175-5357
Emma DempsterDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0003-1257-5314
Clive BallardDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0003-0022-5632
John T O'BrienDepartment of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.ORCID http://orcid.org/0000-0002-0837-5080
Dag AarslandInstitute of Psychiatry, Psychology & Neuroscience (IoPPN), Kings College London, London, UK.ORCID http://orcid.org/0000-0001-6314-216X
Jonathan MillDepartment of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Lasse PihlstrømInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID http://orcid.org/0000-0002-7635-8645
Ehsan Pishva *Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.ORCID http://orcid.org/0000-0002-8964-0682
Katie Lunnon *Department of Clinical and Biomedical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK. k.lunnon@exeter.ac.uk.ORCID http://orcid.org/0000-0001-7570-6065

Funding

A multi-omic approach to elucidate novel disease mechanisms and biomarkers for psychosis in Alzheimer’s diseaseR01AG067015 · NIA · UNIVERSITY OF EXETER · PI KOFLER, JULIA K, LUNNON, KATIE · 2019 to 2023
$1.6M
Alzheimer's Research UK (ARUK) ARUK-PG2023A-037Alzheimer's Society AS-PDF-23-017Alzheimer's Society AS-PG-16b-012Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) MJFF-023152RCUK | Medical Research Council (MRC) G0400074RCUK | Medical Research Council (MRC) MR/M008924/1RCUK | Medical Research Council (MRC) MR/S011625/1U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG067015ZonMw (Netherlands Organisation for Health Research and Development) 733050516
6 · The paper itself

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.

Indexed as

BrainDNA MethylationLewy BodiesLewy Body Diseasealpha-SynucleinCohort StudiesEpigenesis, GeneticGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansParkinson DiseaseQuantitative Trait Locialpha-SynucleinSNCA protein, human

Identifiers

PMID42881165

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.