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Analysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- 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.<br />Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.
- Subjects :
- Epigenomics
Male
0301 basic medicine
Parkinson's disease
General Physics and Astronomy
SLC7A11
0302 clinical medicine
Gene expression
lcsh:Science
Aged, 80 and over
Genetics
DNA methylation
Multidisciplinary
biology
Parkinson Disease
Environmental exposure
Middle Aged
Glutathione
Healthy Volunteers
3. Good health
CpG site
Female
Chromosomes, Human, Pair 4
Adult
Amino Acid Transport System y+
Science
Down-Regulation
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
medicine
Humans
Gene
Aged
Australia
General Chemistry
Mendelian Randomization Analysis
medicine.disease
030104 developmental biology
Risk factors
Case-Control Studies
biology.protein
CpG Islands
lcsh:Q
030217 neurology & neurosurgery
New Zealand
Subjects
Details
- Language :
- English
- ISSN :
- 20411723 and 06690548
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....b3b3c219641bf4df29f9c1acdeaacb72