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    Analysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease (2020)

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    Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinsons disease.pdf (1.708Mb)
    Type of Content
    Journal Article
    UC Permalink
    https://hdl.handle.net/10092/102194
    
    Publisher's DOI/URI
    http://doi.org/10.1038/s41467-020-15065-7
    
    Publisher
    Springer Science and Business Media LLC
    ISSN
    2041-1723
    Language
    eng
    Collections
    • Science: Journal Articles [1104]
    Authors
    Vallerga CL
    Zhang F
    Fowdar J
    McRae AF
    Qi T
    Nabais MF
    Zhang Q
    Kassam I
    Henders AK
    Wallace L
    Montgomery G
    Chuang YH
    Horvath S
    Ritz B
    Halliday G
    Hickie I
    Kwok JB
    Pearson J
    Pitcher T
    Kennedy M
    Bentley SR
    Silburn PA
    Yang J
    Wray NR
    Lewis SJG
    Anderson T
    Mellick GD
    Visscher PM
    Gratten J
    Dalrymple-Alford, John cc
    show all
    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.

    Citation
    Vallerga CL, Zhang F, Fowdar J, McRae AF, Qi T, Nabais MF, Zhang Q, Kassam I, Henders AK, Wallace L, Montgomery G, Chuang YH, Horvath S, Ritz B, Halliday G, Hickie I, Kwok JB, Pearson J, Pitcher T, Kennedy M, Bentley SR, Silburn PA, Yang J, Wray NR, Lewis SJG, Anderson T, Dalrymple-Alford J, Mellick GD, Visscher PM, Gratten J (2020). Analysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease. Nature Communications. 11(1). 1238-.
    This citation is automatically generated and may be unreliable. Use as a guide only.
    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
    ANZSRC Fields of Research
    31 - Biological sciences::3105 - Genetics::310509 - Genomics
    32 - Biomedical and clinical sciences::3209 - Neurosciences::320905 - Neurology and neuromuscular diseases
    Rights
    © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
    http://hdl.handle.net/10092/17651

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