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.
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Abstract
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
Metadata
| 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: | 23 Jun 2025 00:43 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/19663 |
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