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

    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

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    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.",
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    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.

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    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.

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