Table 1 Decision criteria for the identification of 'driver' methylation changes
From: Recommendations for the design and analysis of epigenome-wide association studies
Confidence that methylation difference mediates biological pathway | ||
|---|---|---|
Increase confidence | Decrease confidence | |
Statistical significance | Reaches genome-wide significance | Does not meet predefined significance threshold that takes into account multiple testing |
Effect size (difference in methylation) | Large (>10% difference) | Small (<5% difference) |
Bias and confounding | Bias and confounding are prevented by design or controlled for in the analyses | Bias or uncontrolled confounding may exist and explain the differences observed |
Genomic location | Differential methylation is in a region that may impact regulation of transcription | Current knowledge cannot explain the influence of the observed difference in methylation at that locus on regulation of transcription |
Functional relevance | Affects expression | Does not affect expression |
Biological relevance | Gene codes for known biological function | Biological relevance of DMR location unknown or unrelated to phenotype |
Validation | Findings are replicated in an independent human cohort or animal model using a different technique | No validation of results attempted or results are not replicated in a validation study |
