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

Joshua Harvey; Adam R. Smith; Luke S. Weymouth; Rebecca G. Smith; Isabel Castanho; Leon Hubbard; Byron Creese; Catherine Bresner; Nigel Williams; Ehsan Pishva; Katie Lunnon

doi:10.1038/s41531-025-00877-5

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

Joshua Harvey
, Adam R. Smith
, Luke S. Weymouth
, Rebecca G. Smith
, Isabel Castanho
, Leon Hubbard
, Byron Creese
, Catherine Bresner
, Nigel Williams
, Ehsan Pishva
, Katie Lunnon^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	39
Number of pages	10
Journal	npj Parkinson's Disease
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41531-025-00877-5
Publication status	Published - 2 Mar 2025

Keywords

DEPRESSION
RISK
POPULATION
FEATURES
MOTOR

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Harvey, J., Smith, A. R., Weymouth, L. S., Smith, R. G., Castanho, I., Hubbard, L., Creese, B., Bresner, C., Williams, N., Pishva, E., & Lunnon, K. (2025). Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis. npj Parkinson's Disease, 11(1), Article 39. https://doi.org/10.1038/s41531-025-00877-5

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AU - Castanho, Isabel

AU - Hubbard, Leon

AU - Creese, Byron

AU - Bresner, Catherine

AU - Williams, Nigel

AU - Pishva, Ehsan

AU - Lunnon, Katie

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KW - RISK

KW - POPULATION

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KW - MOTOR

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

Abstract

Keywords

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