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Epigenome-Wide Association Study for Parkinson’s Disease

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Abstract

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® HumanMethylation 450K beadchip (Illumina Inc., USA), twenty unique genes with a sizable difference in methylation (P adjusted < 0.05, Δβ ≥ 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 Δβ values, which have the same direction of effect, are reasonable to warrant further investigation.

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Acknowledgments

A grant was received from the Department of Education and Learning to fund this study. Gen-Probe ran the 450K arrays. The DNA used in the replication phase was historically archived by Dr Owen Ross and Dr Mark Gibson.

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All authors agreed the final version of this manuscript and the authors declare no conflict of interest.

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Ethical approval was granted for this project, and all participants provided informed consent.

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  1. Queens University Belfast, Belfast, UK

    Kerry Moore, Amy Jayne McKnight, David Craig & Francis O’Neill

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  1. Kerry Moore
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  2. Amy Jayne McKnight
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Correspondence to Kerry Moore.

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Moore, K., McKnight, A.J., Craig, D. et al. Epigenome-Wide Association Study for Parkinson’s Disease. Neuromol Med 16, 845–855 (2014). https://doi.org/10.1007/s12017-014-8332-8

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