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

Juan I Young; Sathesh K Sivasankaran; Lily Wang; Aleena Ali; Arpit Mehta; David A Davis; Derek M Dykxhoorn; Carol K Petito; Gary W Beecham; Eden R Martin; Deborah C Mash; Margaret Pericak-Vance; William K Scott; Thomas J Montine; Jeffery M Vance

doi:10.1212/NXG.0000000000000342

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

Journal article

Open access

Peer reviewed

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

Juan I Young, Sathesh K Sivasankaran, Lily Wang, Aleena Ali, Arpit Mehta, David A Davis, Derek M Dykxhoorn, Carol K Petito, Gary W Beecham, Eden R Martin, …

Neurology. Genetics, Vol.5(4), pp.e342-e342

2019-08

DOI: https://doi.org/10.1212/NXG.0000000000000342

PMCID: PMC6659138

PMID: 31403079

Abstract

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. 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. 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 < 0.05). Pathway analysis of these genes showed significant enrichment for the Wnt signaling pathway (FDR < 0.01). 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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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.67 Parkinson's Disease
Web Of Science research areas: Clinical Neurology; Genetics & Heredity
ESI research areas: Neuroscience & Behavior

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Title: Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease
Creators: Juan I Young - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Sathesh K Sivasankaran - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Lily Wang - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Aleena Ali - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Arpit Mehta - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
David A Davis - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Derek M Dykxhoorn - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Carol K Petito - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Gary W Beecham - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Eden R Martin - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Deborah C Mash - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Margaret Pericak-Vance - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
William K Scott - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Thomas J Montine - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Jeffery M Vance - John P. Hussman Institute for Human Genomics (J.I.Y., S.K.S., A.A., A.M., D.M.D., G.W.B., E.R.M., M.P.-V., W.K.S., J.M.V.), Miller School of Medicine, University of Miami; Department of Public Health Sciences (L.W.), Division of Biostatistics, Miller School of Medicine, University of Miami; Department of Neurology (D.A.D., D.C.M.), Miller School of Medicine, University of Miami; Department of Pathology (C.K.P.), Miller School of Medicine, University of Miami, FL; and Department of Pathology (T.J.M.), Stanford University, CA
Publication Details: Neurology. Genetics, Vol.5(4), pp.e342-e342
Publisher: United States
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Department of Neurology; UMMG Department of Pathology; UMMG Department of Public Health Sciences Research; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 31403079
PMCID: PMC6659138
Record Identifier: 991031575968702976