Abstract
A differentially methylated region (DMR) is a genomic region in which DNA methylation is consistently positively or negatively associated with a phenotype or exposure. We demonstrate that existing algorithms for identifying DMRs either fail to consistently control false positive rates (comb-p and DMRcate), suffer from low power (bumphunter) or lack modeling flexibility (seqlm). We introduce a new method, dmrff, that overcomes these shortcomings and can additionally be used to meta-analyze multiple datasets. When applied to investigate associations of age in multiple datasets, dmrff identifies novel DMRs near genes previously linked to age. An R implementation is available on Github (http://github.com/perishky/dmrff).
List of Abbreviations
- CpG
- Cytosine followed by a Guanine
- DMR
- Differentially Methylated Region
- EPIC
- Illumina Infinium MethylationEPIC BeadChip microarray
- EWAS
- Epigenome-Wide Association Study
- FPR
- False Positive Rate
- GEO
- Gene Expression Omnibus
- 450k
- Illumina Infinium HumanMethylation450 BeadChip microarray
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.