DNA methylation changes associated with Parkinson’s disease progression

outcomes from the first longitudinal genome-wide methylation analysis in blood

Harvard Biomarkers Study investigators are listed in the Acknowledgement section

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Parkinson’s Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified by both environment and disease pathophysiology, are emerging as important components of neurodegeneration. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, the extent to which methylation changes correlate with disease progression has not yet been reported; nor the degree to which methylation is affected by PD medication. We performed a longitudinal genome-wide methylation study surveying ~850,000 CpG sites in whole blood from 189 well-characterized PD patients and 191 control individuals obtained at baseline and at a follow-up visit ~2 y later. We identified distinct patterns of methylation in PD cases versus controls. Importantly, we identified genomic sites where methylation changes longitudinally as the disease progresses. Moreover, we identified methylation changes associated with PD pathology through the analysis of PD cases that were not exposed to anti-parkinsonian therapy. In addition, we identified methylation sites modulated by exposure to dopamine replacement drugs. These results indicate that DNA methylation is dynamic in PD and changes over time during disease progression. To the best of our knowledge, this is the first longitudinal epigenome-wide methylation analysis for Parkinson’s disease and reveals changes associated with disease progression and in response to dopaminergic medications in the blood methylome.

Original languageEnglish (US)
JournalEpigenetics
DOIs
StatePublished - Jan 1 2019

Fingerprint

DNA Methylation
Methylation
Parkinson Disease
Disease Progression
Genome
Dopamine Agents
Epigenomics
Neurodegenerative Diseases
Early Diagnosis
Patient Care
Biomarkers
Pathology

Keywords

  • biomarkers
  • blood epigenome
  • disease progression
  • DNA methylation
  • dopamine replacement therapy
  • longitudinal
  • one-carbon metabolism
  • Parkinson’s disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

DNA methylation changes associated with Parkinson’s disease progression : outcomes from the first longitudinal genome-wide methylation analysis in blood. / Harvard Biomarkers Study investigators are listed in the Acknowledgement section.

In: Epigenetics, 01.01.2019.

Research output: Contribution to journalArticle

@article{342f1a07f6c14e4db5e1a9a9c2fce823,
title = "DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood",
abstract = "Parkinson’s Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified by both environment and disease pathophysiology, are emerging as important components of neurodegeneration. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, the extent to which methylation changes correlate with disease progression has not yet been reported; nor the degree to which methylation is affected by PD medication. We performed a longitudinal genome-wide methylation study surveying ~850,000 CpG sites in whole blood from 189 well-characterized PD patients and 191 control individuals obtained at baseline and at a follow-up visit ~2 y later. We identified distinct patterns of methylation in PD cases versus controls. Importantly, we identified genomic sites where methylation changes longitudinally as the disease progresses. Moreover, we identified methylation changes associated with PD pathology through the analysis of PD cases that were not exposed to anti-parkinsonian therapy. In addition, we identified methylation sites modulated by exposure to dopamine replacement drugs. These results indicate that DNA methylation is dynamic in PD and changes over time during disease progression. To the best of our knowledge, this is the first longitudinal epigenome-wide methylation analysis for Parkinson’s disease and reveals changes associated with disease progression and in response to dopaminergic medications in the blood methylome.",
keywords = "biomarkers, blood epigenome, disease progression, DNA methylation, dopamine replacement therapy, longitudinal, one-carbon metabolism, Parkinson’s disease",
author = "{Harvard Biomarkers Study investigators are listed in the Acknowledgement section} and Adrienne Henderson-Smith and Fisch, {Kathleen M.} and Jianping Hua and Ganqiang Liu and Eugenia Ricciardelli and Kristen Jepsen and Mathew Huentelman and Gabriel Stalberg and Edland, {Steven D.} and Scherzer, {Clemens R.} and Travis Dunckley and Paula Desplats",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/15592294.2019.1588682",
language = "English (US)",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Landes Bioscience",

}

TY - JOUR

T1 - DNA methylation changes associated with Parkinson’s disease progression

T2 - outcomes from the first longitudinal genome-wide methylation analysis in blood

AU - Harvard Biomarkers Study investigators are listed in the Acknowledgement section

AU - Henderson-Smith, Adrienne

AU - Fisch, Kathleen M.

AU - Hua, Jianping

AU - Liu, Ganqiang

AU - Ricciardelli, Eugenia

AU - Jepsen, Kristen

AU - Huentelman, Mathew

AU - Stalberg, Gabriel

AU - Edland, Steven D.

AU - Scherzer, Clemens R.

AU - Dunckley, Travis

AU - Desplats, Paula

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Parkinson’s Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified by both environment and disease pathophysiology, are emerging as important components of neurodegeneration. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, the extent to which methylation changes correlate with disease progression has not yet been reported; nor the degree to which methylation is affected by PD medication. We performed a longitudinal genome-wide methylation study surveying ~850,000 CpG sites in whole blood from 189 well-characterized PD patients and 191 control individuals obtained at baseline and at a follow-up visit ~2 y later. We identified distinct patterns of methylation in PD cases versus controls. Importantly, we identified genomic sites where methylation changes longitudinally as the disease progresses. Moreover, we identified methylation changes associated with PD pathology through the analysis of PD cases that were not exposed to anti-parkinsonian therapy. In addition, we identified methylation sites modulated by exposure to dopamine replacement drugs. These results indicate that DNA methylation is dynamic in PD and changes over time during disease progression. To the best of our knowledge, this is the first longitudinal epigenome-wide methylation analysis for Parkinson’s disease and reveals changes associated with disease progression and in response to dopaminergic medications in the blood methylome.

AB - Parkinson’s Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified by both environment and disease pathophysiology, are emerging as important components of neurodegeneration. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, the extent to which methylation changes correlate with disease progression has not yet been reported; nor the degree to which methylation is affected by PD medication. We performed a longitudinal genome-wide methylation study surveying ~850,000 CpG sites in whole blood from 189 well-characterized PD patients and 191 control individuals obtained at baseline and at a follow-up visit ~2 y later. We identified distinct patterns of methylation in PD cases versus controls. Importantly, we identified genomic sites where methylation changes longitudinally as the disease progresses. Moreover, we identified methylation changes associated with PD pathology through the analysis of PD cases that were not exposed to anti-parkinsonian therapy. In addition, we identified methylation sites modulated by exposure to dopamine replacement drugs. These results indicate that DNA methylation is dynamic in PD and changes over time during disease progression. To the best of our knowledge, this is the first longitudinal epigenome-wide methylation analysis for Parkinson’s disease and reveals changes associated with disease progression and in response to dopaminergic medications in the blood methylome.

KW - biomarkers

KW - blood epigenome

KW - disease progression

KW - DNA methylation

KW - dopamine replacement therapy

KW - longitudinal

KW - one-carbon metabolism

KW - Parkinson’s disease

UR - http://www.scopus.com/inward/record.url?scp=85063076689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063076689&partnerID=8YFLogxK

U2 - 10.1080/15592294.2019.1588682

DO - 10.1080/15592294.2019.1588682

M3 - Article

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

ER -