Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 08 2022
22 08 2022
Historique:
received:
17
10
2021
accepted:
09
08
2022
entrez:
22
8
2022
pubmed:
23
8
2022
medline:
25
8
2022
Statut:
epublish
Résumé
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP. Differentially methylated probes were independent of known PD genetic risk alleles. Meta-analysis provided suggestive evidence for a differentially methylated locus within the chromosomal region affected by the PD-associated 22q11.2 deletion. Our findings elucidate novel disease pathways in PD and DLB and generate hypotheses for future molecular studies of Lewy body pathology.
Identifiants
pubmed: 35995800
doi: 10.1038/s41467-022-32619-z
pii: 10.1038/s41467-022-32619-z
pmc: PMC9395387
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4932Subventions
Organisme : Medical Research Council
ID : MR/W004984/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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