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Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease

OBJECTIVE: Given the known strong relationship of DNA methylation with environmental exposure, we investigated whether brain regions affected in Parkinson disease (PD) were differentially methylated between PD cases and controls. METHODS: DNA chip arrays were used to perform a genome-wide screen of...

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Autores principales: Young, Juan I., Sivasankaran, Sathesh K., Wang, Lily, Ali, Aleena, Mehta, Arpit, Davis, David A., Dykxhoorn, Derek M., Petito, Carol K., Beecham, Gary W., Martin, Eden R., Mash, Deborah C., Pericak-Vance, Margaret, Scott, William K., Montine, Thomas J., Vance, Jeffery M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659138/
https://www.ncbi.nlm.nih.gov/pubmed/31403079
http://dx.doi.org/10.1212/NXG.0000000000000342
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author Young, Juan I.
Sivasankaran, Sathesh K.
Wang, Lily
Ali, Aleena
Mehta, Arpit
Davis, David A.
Dykxhoorn, Derek M.
Petito, Carol K.
Beecham, Gary W.
Martin, Eden R.
Mash, Deborah C.
Pericak-Vance, Margaret
Scott, William K.
Montine, Thomas J.
Vance, Jeffery M.
author_facet Young, Juan I.
Sivasankaran, Sathesh K.
Wang, Lily
Ali, Aleena
Mehta, Arpit
Davis, David A.
Dykxhoorn, Derek M.
Petito, Carol K.
Beecham, Gary W.
Martin, Eden R.
Mash, Deborah C.
Pericak-Vance, Margaret
Scott, William K.
Montine, Thomas J.
Vance, Jeffery M.
author_sort Young, Juan I.
collection PubMed
description OBJECTIVE: Given the known strong relationship of DNA methylation with environmental exposure, we investigated whether brain regions affected in Parkinson disease (PD) were differentially methylated between PD cases and controls. METHODS: DNA chip arrays were used to perform a genome-wide screen of DNA methylation on the dorsal motor nucleus of the vagus (DMV), substantia nigra (SN), and cingulate gyrus (CG) of pathologically confirmed PD cases and controls selected using the criteria of Beecham et al. Analysis examined differentially methylated regions (DMRs) between cases and controls for each brain area. RNA sequencing and pathway analysis were also performed for each brain area. RESULTS: Thirty-eight PD cases and 41 controls were included in the analysis. Methylation studies revealed 234 significant DMR in the DMV, 44 in the SN, and 141 in the CG between cases and controls (Sidak p < 0.05). Pathway analysis of these genes showed significant enrichment for the Wnt signaling pathway (FDR < 0.01). CONCLUSIONS: Our data suggest that significant DNA methylation changes exist between cases and controls in PD, especially in the DMV, one of the areas affected earliest in PD. The etiology of these methylation changes is not yet known, but the predominance of methylation changes occurring in the DMV supports the hypothesis that vagus nerve function, perhaps involving the gastrointestinal system, is important in PD pathogenesis. These data also give independent support that genes involved in Wnt signaling are a likely factor in the neurodegenerative processes of PD.
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spelling pubmed-66591382019-08-09 Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease Young, Juan I. Sivasankaran, Sathesh K. Wang, Lily Ali, Aleena Mehta, Arpit Davis, David A. Dykxhoorn, Derek M. Petito, Carol K. Beecham, Gary W. Martin, Eden R. Mash, Deborah C. Pericak-Vance, Margaret Scott, William K. Montine, Thomas J. Vance, Jeffery M. Neurol Genet Article OBJECTIVE: Given the known strong relationship of DNA methylation with environmental exposure, we investigated whether brain regions affected in Parkinson disease (PD) were differentially methylated between PD cases and controls. METHODS: DNA chip arrays were used to perform a genome-wide screen of DNA methylation on the dorsal motor nucleus of the vagus (DMV), substantia nigra (SN), and cingulate gyrus (CG) of pathologically confirmed PD cases and controls selected using the criteria of Beecham et al. Analysis examined differentially methylated regions (DMRs) between cases and controls for each brain area. RNA sequencing and pathway analysis were also performed for each brain area. RESULTS: Thirty-eight PD cases and 41 controls were included in the analysis. Methylation studies revealed 234 significant DMR in the DMV, 44 in the SN, and 141 in the CG between cases and controls (Sidak p < 0.05). Pathway analysis of these genes showed significant enrichment for the Wnt signaling pathway (FDR < 0.01). CONCLUSIONS: Our data suggest that significant DNA methylation changes exist between cases and controls in PD, especially in the DMV, one of the areas affected earliest in PD. The etiology of these methylation changes is not yet known, but the predominance of methylation changes occurring in the DMV supports the hypothesis that vagus nerve function, perhaps involving the gastrointestinal system, is important in PD pathogenesis. These data also give independent support that genes involved in Wnt signaling are a likely factor in the neurodegenerative processes of PD. Wolters Kluwer 2019-06-24 /pmc/articles/PMC6659138/ /pubmed/31403079 http://dx.doi.org/10.1212/NXG.0000000000000342 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Young, Juan I.
Sivasankaran, Sathesh K.
Wang, Lily
Ali, Aleena
Mehta, Arpit
Davis, David A.
Dykxhoorn, Derek M.
Petito, Carol K.
Beecham, Gary W.
Martin, Eden R.
Mash, Deborah C.
Pericak-Vance, Margaret
Scott, William K.
Montine, Thomas J.
Vance, Jeffery M.
Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title_full Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title_fullStr Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title_full_unstemmed Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title_short Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
title_sort genome-wide brain dna methylation analysis suggests epigenetic reprogramming in parkinson disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659138/
https://www.ncbi.nlm.nih.gov/pubmed/31403079
http://dx.doi.org/10.1212/NXG.0000000000000342
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