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

Epigenetics ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. 365-382 ◽  
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

scholarly journals Butyrate and related epigenetic changes link Parkinson's disease to inflammatory bowel disease and depressive symptoms

2021 ◽  
Author(s):  
Aoji Xie ◽  
Elizabeth Ensink ◽  
Peipei Li ◽  
Juozas Gordevicius ◽  
Lee L. Marshall ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Depressive Symptoms ◽  
Gut Microbiome ◽  
Whole Blood ◽  
Blood Samples ◽  
Targeted Bisulfite Sequencing ◽  
Genome Wide ◽  
Whole Blood Samples

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.

scholarly journals 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

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.

scholarly journals 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

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.

scholarly journals Genome-wide association study of Parkinson’s disease progression biomarkers in 12 longitudinal patients’ cohorts

2019 ◽  
Author(s):  
Hirotaka Iwaki ◽  
Cornelis Blauwendraat ◽  
Hampton L. Leonard ◽  
Jonggeol J. Kim ◽  
Ganqiang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
P Value ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome

AbstractBackgroundSeveral reports have identified different patterns of Parkinson’s disease progression in individuals carrying missense variants in theGBAorLRRK2genes. The overall contribution of genetic factors to the severity and progression of Parkinson’s disease, however, has not been well studied.ObjectivesTo test the association between genetic variants and the clinical features and progression of Parkinson’s disease on a genome-wide scale.MethodsWe accumulated individual data from 12 longitudinal cohorts in a total of 4,093 patients with 25,254 observations over a median of 3.81 years. Genome-wide associations were evaluated for 25 cross-sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently-identified disease risk variants, were also investigated for the associations with these phenotypes.ResultsTwo variants were genome-wide significant. Rs382940(T>A), within the intron ofSLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (HR 2.04 [1.58, 2.62], P-value = 3.46E-8). Rs61863020(G>A), an intergenic variant and eQTL forADRA2A, was associated with a lower prevalence of insomnia at baseline (OR 0.63 [0,52, 0.75], P-value = 4.74E-8). In the targeted analysis, we found nine associations between known Parkinson’s risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports ofGBAcoding variants (rs2230288: p.E365K, rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, andAPOEE4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.ConclusionsWe identified novel genetic factors associated with heterogeneity of progression in Parkinson’s disease. The results provide new insights into the pathogenesis of Parkinson’s disease as well as patient stratification for clinical trials.

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

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.

Sign in / Sign up

Export Citation Format

Share Document