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research article

Common genetic variants associated with Parkinson's disease display widespread signature of epigenetic plasticity

Sharma, Amit
•
Osato, Naoki
•
Liu, Hongde
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December 5, 2019
Scientific Reports

Parkinson disease (PD) is characterized by a pivotal progressive loss of substantia nigra dopaminergic neurons and aggregation of alpha-synuclein protein encoded by the SNCA gene. Genome-wide association studies identified almost 100 sequence variants linked to PD in SNCA. However, the consequences of this genetic variability are rather unclear. Herein, our analysis on selective single nucleotide polymorphisms (SNPs) which are highly associated with the PD susceptibility revealed that several SNP sites attribute to the nucleosomes and overlay with bivalent regions poised to adopt either active or repressed chromatin states. We also identified large number of transcription factor (TF) binding sites associated with these variants. In addition, we located two docking sites in the intron-1 methylation prone region of SNCA which are required for the putative interactions with DNMT1. Taken together, our analysis reflects an additional layer of epigenomic contribution for the regulation of the SNCA gene in PD.

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Type
research article
DOI
10.1038/s41598-019-54865-w
Web of Science ID

WOS:000501569500001

Author(s)
Sharma, Amit
Osato, Naoki
Liu, Hongde
Asthana, Shailendra
Dakal, Tikam Chand
Ambrosini, Giovanna  
Bucher, Philipp  
Schmitt, Ina
Wuellner, Ullrich
Date Issued

2019-12-05

Publisher

Springer Nature

Published in
Scientific Reports
Volume

9

Article Number

18464

Subjects

Multidisciplinary Sciences

•

Science & Technology - Other Topics

•

alpha-synuclein expression

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genome-wide association

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identification

•

transcription

•

metaanalysis

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methylation

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promoter

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sequence

•

site

Note

This article is licensed under a Creative Commons Attribution 4.0 International License

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
GR-BUCHER  
Available on Infoscience
December 25, 2019
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/164180
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