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

Amit Sharma, Naoki Osato, Hongde Liu, Shailendra Asthana, Tikam Chand Dakal, Giovanna Ambrosini, Philipp Bucher, Ina Schmitt, Ullrich Wüllner

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Parkinson disease (PD) is characterized by a pivotal progressive loss of substantia nigra dopaminergic neurons and aggregation of α-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.

Original languageEnglish
Article number18464
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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