Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis.

Harvey, Joshua, Smith, Adam R., Weymouth, Luke S., Smith, Rebecca G., Castanho, Isabel, Hubbard, Leon, Creese, Byron, Bresner, Catherine ORCID: https://orcid.org/0000-0003-2673-9762, Williams, Nigel ORCID: https://orcid.org/0000-0003-1177-6931, Pishva, Ehsan and Lunnon, Katie 2025. Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis. npj Parkinson's Disease 11 (1) , p. 39. 10.1038/s41531-025-00877-5

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Abstract

Parkinson's disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinson's disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. Of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regards to depressive symptoms in Parkinson's disease.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: Title: cc by, Type: cc by
Publisher:	Nature Research
Date of First Compliant Deposit:	17 March 2025
Date of Acceptance:	24 January 2025
Last Modified:	05 Jun 2025 11:14
URI:	https://orca.cardiff.ac.uk/id/eprint/176916

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