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Neurogenetics
Published in: neurogenetics 1/2017

01-01-2017 | Original Article

Epigenome-wide DNA methylation analysis in siblings and monozygotic twins discordant for sporadic Parkinson’s disease revealed different epigenetic patterns in peripheral blood mononuclear cells

Authors: Oliver Kaut, Ina Schmitt, Jörg Tost, Florence Busato, Yi Liu, Per Hofmann, Stephanie H. Witt, Marcella Rietschel, Holger Fröhlich, Ullrich Wüllner

Published in: Neurogenetics | Issue 1/2017

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Abstract

Numerous studies have elucidated the genetics of Parkinson’s disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs. 227 healthy individuals (cohort 1) applying Illumina’s VeraCode and 472 PD patients vs. 487 controls (cohort 2) using pyrosequencing. We choose a delta beta of >15 % and selected 62 differentially methylated CpGs in 51 genes from the discordant siblings. Among them, three displayed multiple CpGs per gene: microRNA 886 (MIR886, 10 CpGs), phosphodiesterase 4D (PDE4D, 2 CpGs) and tripartite motif-containing 34 (TRIM34, 2 CpGs). PDE4D was confirmed in both cohorts (p value 2.44e−05). In addition, for biomarker construction, we used the penalized logistic regression model, resulting in a signature of eight CpGs with an AUC of 0.77. Our findings suggest that a distinct level of PD susceptibility stems from individual, epigenetic modifications of specific genes. We identified a signature of CpGs in blood cells that could separate control from disease with a reasonable discriminatory power, holding promise for future epigenetically based biomarker development.
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Metadata
Title
Epigenome-wide DNA methylation analysis in siblings and monozygotic twins discordant for sporadic Parkinson’s disease revealed different epigenetic patterns in peripheral blood mononuclear cells
Authors
Oliver Kaut
Ina Schmitt
Jörg Tost
Florence Busato
Yi Liu
Per Hofmann
Stephanie H. Witt
Marcella Rietschel
Holger Fröhlich
Ullrich Wüllner
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Neurogenetics / Issue 1/2017
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-016-0497-x

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