Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinson's disease.

Nature Communications
Costanza L VallergaJacob Gratten

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.

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Citations

Jul 8, 2020·International Journal of Molecular Sciences·Aintzane Urbizu, Katrin Beyer
Feb 5, 2021·Signal Transduction and Targeted Therapy·Hong-Fa YanPeng Lei
Feb 5, 2021·Ageing Research Reviews·P A DionísioC M P Rodrigues
Jan 12, 2021·Frontiers in Genetics·Junkai XieChongli Yuan
Feb 5, 2021·Frontiers in Cell and Developmental Biology·Collin M BantleEvgeny Shlevkov
Jul 30, 2020·Progress in Neurobiology·Laura Mahoney-SánchezJean-Christophe Devedjian
May 25, 2021·Frontiers in Endocrinology·Patrycja MulicaSandro L Pereira
Jul 29, 2021·Neuropathology and Applied Neurobiology·Megha MurthyConceição Bettencourt
Sep 28, 2021·Antioxidants & Redox Signaling·Samuel DavidAntje Kroner

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Software Mentioned

MOA
R meffil
OSCA
R meffil package
Brain
MOMENT
MWAS
OREML
MOMENT MWAS
GCTA

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