Table 1. Main issues to consider when appraising the validity and importance of epigenetic association studies (based on Riancho20).
| Domain | Key items |
|---|---|
| Study validity | 1. Subjects |
| •Age and sex | |
| •Diagnostic criteria, disease stage and prior therapy | |
| •Appropriateness of controls | |
| 2. Tissue | |
| •Relevance for disease pathogenesis | |
| •Heterogeneity of cell composition | |
| 3. Technology and data analysis | |
| •Epigenome coverage | |
| •Precision and accuracy | |
| •Statistical errors | |
| Main results | 1. Analysis of association with phenotype |
| •Single locus | |
| •Genomic regions (promoters, enhancers, TFBSs etc.) | |
| 2. Gene network analysis | |
| •Molecular interaction networks | |
| •Pathways | |
| •Other (GSEA, miRNA families etc.) | |
| 3. Functional assays | |
| •In silico | |
| •In vitro | |
| •In vivo | |
| Study importance | 1. Biological rationale |
| 2. Replication in independent populations | |
| 3. Direction of effect (causality and reverse causality) | |
| 4. Practical relevance | |
| •Biomarkers | |
| •Disease pathogenesis | |
| •Direct and indirect therapeutic targets |
Abbreviations: GSEA, gene set enrichment analysis; miRNA, microRNA; TFBS, transcription factor-binding site.