Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

An improved understanding of etiological mechanisms in Parkinson's disease (PD) is urgently needed because the number of affected individuals is projected to increase rapidly as populations age. We present results from a blood-based methylome-wide association study of PD involving meta-analysis of 229 K CpG probes in 1,132 cases and 999 controls from two independent cohorts. We identify two previously unreported epigenome-wide significant associations with PD, including cg06690548 on chromosome 4. We demonstrate that cg06690548 hypermethylation in PD is associated with down-regulation of the SLC7A11 gene and show this is consistent with an environmental exposure, as opposed to medications or genetic factors with effects on DNA methylation or gene expression. These findings are notable because SLC7A11 codes for a cysteine-glutamate anti-porter regulating levels of the antioxidant glutathione, and it is a known target of the environmental neurotoxin β-methylamino-L-alanine (BMAA). Our study identifies the SLC7A11 gene as a plausible biological target in PD.

Original publication

DOI

10.1038/s41467-020-15065-7

Type

Journal article

Journal

Nature communications

Publication Date

03/2020

Volume

11

Addresses

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.

Keywords

Chromosomes, Human, Pair 4, Humans, Parkinson Disease, Glutathione, Amino Acid Transport System y+, Case-Control Studies, DNA Methylation, Down-Regulation, CpG Islands, Adult, Aged, Aged, 80 and over, Middle Aged, Australia, New Zealand, Female, Male, Mendelian Randomization Analysis, Epigenomics, Healthy Volunteers