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Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology

Lookup NU author(s): Professor Alan ThomasORCiD

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Abstract

© 2022. The Author(s). 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.

Publication metadata

Author(s): Pihlstrom L, Shireby G, Geut H, Henriksen SP, Rozemuller AJM, Tunold J-A, Hannon E, Francis P, Thomas AJ, Love S, Mill J, van de Berg WDJ, Toft M

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2022

Volume: 13

Issue: 1

Online publication date: 22/08/2022

Acceptance date: 09/08/2022

Date deposited: 05/09/2022

ISSN (electronic): 2041-1723

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41467-022-32619-z

DOI: 10.1038/s41467-022-32619-z

PubMed id: 35995800

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