Epigenome-wide Association Study of Human Frontal Cortex Identifies Differential Methylation in Lewy Body Pathology

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 22

PMID 35995800

Authors

Lasse Pihlstrom

Gemma Shireby

Hanneke Geut

Sandra Pilar Henriksen

Annemieke J M Rozemuller

Jon-Anders Tunold

Eilis Hannon

Paul Francis

Alan J Thomas

Seth Love

Jonathan Mill

Wilma D J van de Berg

Mathias Toft

Affiliations

Soon will be listed here.

Abstract

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.

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