Evidence map›Paper›PMID 41033114›Full record

ArticleParkinsonism & related disorders2025

Epigenomic profile of GBA1 in Parkinson's disease.

Eloise Berson, Raphael Zaghroun, Matteo Santoro, Syed Bukhari, David Seong, Chi-Hung Shu, Amalia Perna, Tomin James, Kathleen S Montine, Geidy E Serrano and 7 more

Abstract read
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In one paragraph

Article in Parkinsonism & related disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

17 authors.

Eloise BersonDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 300 Pasteur Drive H3580, Stanford, CA, 94305, USA; Department of Biomedical Data Science, Stanford University, 300 Pasteur Drive R348, Stanford, CA, USA.
Raphael ZaghrounDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.
Matteo SantoroDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.
Syed BukhariDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.
David SeongDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 300 Pasteur Drive H3580, Stanford, CA, 94305, USA; Immunology Program, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.
Chi-Hung ShuDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 300 Pasteur Drive H3580, Stanford, CA, 94305, USA; Department of Biomedical Data Science, Stanford University, 300 Pasteur Drive R348, Stanford, CA, USA; Department of Pediatrics - Neonatal and Developmental Medicine, Stanford University, 453 Quarry Road, Stanford, CA, USA.
Amalia PernaDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.
Tomin JamesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 300 Pasteur Drive H3580, Stanford, CA, 94305, USA; Department of Biomedical Data Science, Stanford University, 300 Pasteur Drive R348, Stanford, CA, USA.
Kathleen S MontineDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.
Geidy E SerranoDepartment of Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ, 85351, USA.
Thomas G BeachDepartment of Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ, 85351, USA.
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, 1959 NE Pacific St. Box 356100., Seattle, WA, 98195, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA, 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, 327 Campus Drive, Stanford, CA, 94305, USA.
M Ryan CorcesGladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA, 94158, USA; Gladstone Institute of Data Science and Biotechnology, 1650 Owens Street, San Francisco, CA, 94158, USA; Department of Neurology, University of California San Francisco, 16514(th) ST, Suite 212, San Francisco, CA, 94518, USA.
Brenna CholertonDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA. Electronic address: bchol@stanford.edu.
Nima AghaeepourDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 300 Pasteur Drive H3580, Stanford, CA, 94305, USA; Department of Biomedical Data Science, Stanford University, 300 Pasteur Drive R348, Stanford, CA, USA; Immunology Program, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.
Thomas J MontineDepartment of Pathology, Stanford University, 300 Pasteur Drive L235, Stanford, CA, 94305, USA.

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI GONZALEZ HERNANDEZ, GRACIELA · 2001 to 2020
$32.5M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI SUMAN JAYADEV · 2020 to 2026
$29.0M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI HEATHER Allyson BIMONTE-NELSON · 2021 to 2026
$24.9M
Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omicsP01AG073082 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2021 to 2025
$23.4M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologiesU01AG072573 · NIA · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2021 to 2025
$8.3M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
Machine Learning for Integrative Modeling of the Immune System in Clinical SettingsR35GM138353 · NIGMS · STANFORD UNIVERSITY · PI AGHAEEPOUR, NIMA · 2020 to 2024
$2.2M
Neuropathology of synapses in AD and ADRDRF1AG077443 · NIA · STANFORD UNIVERSITY · PI AGHAEEPOUR, NIMA, MONTINE, THOMAS J · 2023 to 2023
$2.2M
NHGRI NIH HHS RM1 HG007735NIA NIH HHS P01 AG073082NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG072980NIA NIH HHS RF1 AG077443NIA NIH HHS U01 AG072573NIGMS NIH HHS R35 GM138353NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

introductionWhile genome-wide association studies have identified GBA1 as a key gene contributing to disease severity and cognitive decline in PD, its molecular effects remain poorly understood.

methodsWe used integrative bulk ATAC-seq across six brain regions from autopsied individuals with PD and varying genetic risk to characterize region- and cell type-specific molecular differences. Using Cellformer, an AI-based bulk ATAC-seq-deconvolution tool, we determined cell type-specific effects of GBA1 on PD disease progression and then validated our findings using whole transcriptome data from blood samples.

resultsEpigenomic differences between PD with ("GBA+"; n = 15) and without ("GBA-", n = 15) GBA1 variants were localized in substantia nigra. Nineteen chromatin-accessible regions strictly separated GBA+ from GBA-, including the promoter sites of key genes such as CACNA1C, EHMT1, and SLC25A48. The effect in GBA + spanned the main cell types in brain, and chromatin differences between GBA- and GBA + increased with neuropathologic progression of disease. Significant differences in the epigenomic profile in GBA+ were observed in neuronal cells (AUROC = 0.8, AUPRC = 0.8, P-value<0.0001). Validation in blood samples distinguished between GBA+ and GBA-subtypes, achieving AUROC values of 0.99. Over 5000 transcripts in blood cells distinguished GBA+ from GBA-, validating key genes and pathways from our epigenomic analysis of brain regions.

conclusionOur study provides novel insights into the cell type-specific epigenomic and transcriptomic landscape of GBA+ and its molecular divergence from other PD subtypes, and highlights potential therapeutic targets for this genetically defined subset of PD.

Indexed as

beta-GlucosidaseEpigenesis, GeneticGlucosylceramidaseParkinson DiseaseAgedDisease ProgressionEpigenomicsFemaleHumansMaleMiddle AgedSubstantia Nigrabeta-GlucosidaseGBA protein, humanGlucosylceramidaseEpigenomicGBAGeneticsParkinson's disease

Identifiers

PMID41033114
PMCPMC12825421

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