Genome-wide DNA methylation and Organophosphate pesticide exposure in Central California Parkinson’s disease patients and healthy controls

Background The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. Here, we investigate whether the changes in the gut microbiome and associated metabolites are linked to PD symptoms and epigenetic markers in leucocytes and neurons. Methods Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified the genome-wide DNA methylation by targeted bisulfite sequencing. Results We show that lower fecal butyrate and reduced Roseburia, Romboutsia, and Prevotella counts are linked to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA (mDNA) regions in PD overlap with those altered in gastrointestinal, autoimmune, and psychiatric diseases.

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Organophosphate Pesticide Exposure, Differential Genome-Wide DNA Methylation, and Biologic Function

ISEE Conference Abstracts ◽

10.1289/isesisee.2018.o01.02.26 ◽

2018 ◽

Vol 2018 (1) ◽

Author(s):

Kimberly C Paul ◽

Yu-Hsuan Chuang ◽

Myles Cockburn ◽

Jeff Bronstein ◽

Steve Horvath ◽

...

Keyword(s):

Dna Methylation ◽

Pesticide Exposure ◽

Organophosphate Pesticide ◽

Genome Wide ◽

Biologic Function

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No differential DNA methylation of PARK2 in brain of Parkinson's disease patients and healthy controls

Movement Disorders ◽

10.1002/mds.25593 ◽

2013 ◽

Vol 28 (14) ◽

pp. 2032-2033 ◽

Cited By ~ 7

Author(s):

Lorena De Mena ◽

Lucía F. Cardo ◽

Eliecer Coto ◽

Victoria Alvarez ◽

Eliecer Coto

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Healthy Controls

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Genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson’s Disease and exposure to organochlorines reveal glial genes and pathways involved in neurotoxicity

10.21203/rs.2.15308/v1 ◽

2019 ◽

Author(s):

Rodney C.P. Go ◽

Michael J Corley ◽

George Webster Ross ◽

Helen Petrovich ◽

Kamal H Masaki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Epidemiological Studies ◽

Postmortem Brain ◽

Genome Wide ◽

Proinflammatory Responses ◽

The Central Nervous System ◽

Pathway Analyses ◽

Humanmethylation450k Beadchip

Abstract Background: Parkinson’s Disease (PD) is a disease of the central nervous system that progressively affects the motor system. Epidemiological studies have provided evidence that exposure to agriculture-related occupations or agrichemicals elevate a person’s risk for PD. Here, we sought to examine the possible epigenetic changes associated with working on a plantation on Oahu, HI and/or exposure to organochlorines (OGC) in PD cases. Results: We measured genome-wide DNA methylation using the Illumina Infinium HumanMethylation450K BeadChip array in matched peripheral blood and postmortem brain biospecimens in PD cases (n=21) assessed for years of plantation work and presence of organochlorines in brain tissue. The comparison of 10+ to 0 years of plantation work exposure detected 7 and 123 differentially methylated loci (DML) in brain and blood DNA, respectively ( P <0.0001). The comparison of cases with 4+ to 0-2 detectable levels of OGC, identified 8 and 18 DML in brain and blood DNA, respectively ( P <0.0001). Pathway analyses revealed links to key neurotoxic and neuropathologic pathways related to impaired immune and proinflammatory responses as well as impaired clearance of damaged proteins, as found in the predominantly glial cell population in these environmental exposure-related PD cases. Conclusions : These results suggest that distinct DNA methylation biomarker profiles related to environmental exposures in PD cases with previous exposure can be found in both brain and blood.

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Organophosphate pesticide exposure and differential genome-wide DNA methylation

The Science of The Total Environment ◽

10.1016/j.scitotenv.2018.07.143 ◽

2018 ◽

Vol 645 ◽

pp. 1135-1143 ◽

Cited By ~ 22

Author(s):

Kimberly C. Paul ◽

Yu-Hsuan Chuang ◽

Myles Cockburn ◽

Jeff M. Bronstein ◽

Steve Horvath ◽

...

Keyword(s):

Dna Methylation ◽

Pesticide Exposure ◽

Organophosphate Pesticide ◽

Genome Wide

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DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood

Epigenetics ◽

10.1080/15592294.2019.1588682 ◽

2019 ◽

Vol 14 (4) ◽

pp. 365-382 ◽

Cited By ~ 16

Author(s):

Adrienne Henderson-Smith ◽

Kathleen M. Fisch ◽

Jianping Hua ◽

Ganqiang Liu ◽

Eugenia Ricciardelli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Disease Progression ◽

Methylation Analysis ◽

Genome Wide

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Genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson’s Disease and exposure to organochlorines reveal possible involvement of glial genes and pathways involved in neurotoxicity

10.21203/rs.2.15308/v2 ◽

2020 ◽

Author(s):

Rodney C.P. Go ◽

Michael J Corley ◽

George Webster Ross ◽

Helen Petrovich ◽

Kamal H Masaki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Epidemiological Studies ◽

Postmortem Brain ◽

Genome Wide ◽

Proinflammatory Responses ◽

The Central Nervous System ◽

Pathway Analyses ◽

Humanmethylation450k Beadchip

Abstract Background: Parkinson’s Disease (PD) is a disease of the central nervous system that progressively affects the motor system. Epidemiological studies have provided evidence that exposure to agriculture-related occupations or agrichemicals elevate a person’s risk for PD. Here, we sought to examine the possible epigenetic changes associated with working on a plantation on Oahu, HI and/or exposure to organochlorines (OGC) in PD cases. Results: We measured genome-wide DNA methylation using the Illumina Infinium HumanMethylation450K BeadChip array in matched peripheral blood and postmortem brain biospecimens in PD cases (n=20) assessed for years of plantation work and presence of organochlorines in brain tissue. The comparison of 10+ to 0 years of plantation work exposure detected 7 and 123 differentially methylated loci (DML) in brain and blood DNA, respectively (P<0.0001). The comparison of cases with 4+ to 0-2 detectable levels of OGC, identified 8 and 18 DML in brain and blood DNA, respectively (P <0.0001). Pathway analyses revealed links to key neurotoxic and neuropathologic pathways related to impaired immune and proinflammatory responses as well as impaired clearance of damaged proteins, as found in the predominantly glial cell population in these environmental exposure-related PD cases.Conclusions: These results suggest that distinct DNA methylation biomarker profiles related to environmental exposures in PD cases with previous exposure can be found in both brain and blood.

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Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2016.08.002 ◽

2016 ◽

Vol 32 ◽

pp. 25-30 ◽

Cited By ~ 19

Author(s):

Joanna M. Biernacka ◽

Sun Ju Chung ◽

Sebastian M. Armasu ◽

Kari S. Anderson ◽

Christina M. Lill ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pesticide Exposure ◽

Interaction Analysis ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment ◽

Genome Wide

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Parkinson’s Disease-Associated, Sex-specific Changes in DNA Methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in Cortical Neurons

10.1101/2021.09.08.459434 ◽

2021 ◽

Author(s):

Joseph Kochmanski ◽

Nathan C. Kuhn ◽

Alison I. Bernstein

Keyword(s):

Parkinson’S Disease ◽

Dna Methylation ◽

Parkinson's Disease ◽

Cortical Neurons ◽

Disease Risk ◽

Neuronal Population ◽

Tissue Samples ◽

Genome Wide ◽

Dna Modifications ◽

The Relationship

AbstractEvidence for epigenetic regulation playing a role in Parkinson’s disease (PD) is growing, particularly for DNA modifications. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA modifications in PD, but none accounted for cell-type or sex in their analyses. Given the hetereogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this first genome-wide analysis of DNA methylation in an enriched neuronal population from PD post-mortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance.

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