BIROn - Birkbeck Institutional Research Online

    Estimation of a significance threshold for epigenome-wide association studies

    Saffari, Ayden and Silver, M.J. and Zavattari, P. and Moi, L. and Columbano, A. and Meaburn, Emma and Dudbridge, F. (2018) Estimation of a significance threshold for epigenome-wide association studies. Genetic Epidemiology 42 (1), pp. 20-33. ISSN 1098-2272.

    Saffari_et_al-2017-Genetic_Epidemiology.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (765kB) | Preview


    Epigenome-wide association studies (EWAS) are designed to characterise population-level epigenetic differences across the genome and link them to disease. Most commonly, they assess DNA-methylation status at cytosine-guanine dinucleotide (CpG) sites, using platforms such as the Illumina 450k array that profile a subset of CpGs genome wide. An important challenge in the context of EWAS is determining a significance threshold for declaring a CpG site as differentially methylated, taking multiple testing into account. We used a permutation method to estimate a significance threshold specifically for the 450k array and a simulation extrapolation approach to estimate a genome-wide threshold. These methods were applied to five different EWAS datasets derived from a variety of populations and tissue types. We obtained an estimate of α=2.4×10-7 for the 450k array, and a genome-wide estimate of α=3.6×10-8. We further demonstrate the importance of these results by showing that previously recommended sample sizes for EWAS should be adjusted upwards, requiring samples between ∼10% and ∼20% larger in order to maintain type-1 errors at the desired level


    Item Type: Article
    Keyword(s) / Subject(s): CpG, DNA methylation, epigenetic epidemiology, EWAS, FWER, GWAS, permutation, resampling, simulation extrapolation
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Psychological Sciences
    Research Centres and Institutes: Brain and Cognitive Development, Centre for (CBCD)
    Depositing User: Emma Meaburn
    Date Deposited: 07 Nov 2017 16:43
    Last Modified: 02 Aug 2023 17:35


    Activity Overview
    6 month trend
    6 month trend

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item