Journal
NEUROMOLECULAR MEDICINE
Volume 16, Issue 4, Pages 845-855Publisher
HUMANA PRESS INC
DOI: 10.1007/s12017-014-8332-8
Keywords
Methylation; Parkinson's disease; Anxiety; Epigenetics; FANCC; TNKS2
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Funding
- Department of Education and Learning
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A methylation-based EWAS on carefully phenotyped individuals with Parkinson's disease (PD) was conducted to reveal prioritised genes and pathways with statistically significant and sizable changes in PD and in the anxiety that often accompanies it. This was followed by subsequent replication of top-ranked CpG sites. Using the Infinium(A (R)) HumanMethylation 450K beadchip (Illumina Inc., USA), twenty unique genes with a sizable difference in methylation (P (adjusted) < 0.05, Delta beta a parts per thousand yen 0.2), after correction for multiple testing, were identified between PD and controls, while seventeen were identified between PD with anxiety and PD without anxiety. Twelve top ranked, significantly associated loci in PD were evaluated in an independent replicate population using Sequenom EpiTYPER for 219 individuals with similar phenotypes to the cross-sectional case-control discovery design. FANCC cg14115740 and TNKS2 cg11963436 show significant differential methylation between PD cases and controls using both techniques and their Delta beta values, which have the same direction of effect, are reasonable to warrant further investigation.
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