Table 1.
Main characteristics of recent large-scale epigenome-wide association studies. All listed studies used the Infinium HumanMethylation450 BeadArray (485,000 CpGs covering all genes). Diff: differentially; DMR: differentially methylated region; EVA-PR: Epigenetic Variation and Childhood Asthma in Puerto Ricans; PIAMA: Prevention and Incidence of Asthma and Mite Allergy birth cohort; SLSJ: Saguenay-Lac-Saint-Jean asthma familial collection (Quebec)
| Study | Allergy | Sample size | Tissue and study design | Main findings | Replication | Comments |
|---|---|---|---|---|---|---|
| Xu et al. [26] | Asthma (2/3 criteria: Doctor diagnosis, recent asthma medication, recent wheezing) | 207 cases vs 610 controls at age 4–5; 185 patients vs 546 controls at age 8 (4 European birth cohorts) | Whole blood/cross-sectional | 27 CpGs including LMAN2, STX3, LPIN1, DICER1 |
247 cases and 2949 controls (seven cohorts) 14/14 CpGs replicated |
DNA methylation changes correlated with eosinophil numbers, more pronounced DNA methylation changes in isolated eosinophils |
| Reese et al. [27] | Asthma (doctor diagnosis and current or recent asthma episode or recent asthma medication) | 631 cases vs 2231 controls 7–17 years (9 cohorts) | PBMCs/cross-sectional | 179 CpGs and 36 regions including ZFPM1 and IL5RA | Meta-analysis, changes replicated in purified eosinophils (SLSJ cohort) | Largest meta-analysis so far, includes cohorts of mixed and African American ancestry |
| 668 cases vs 2904 controls at birth | Cord blood/prospective | 9 CpGs associated with: CLNS1A, miR548, GPATCH2, LOC100129858, AK091866, SUB1, WDR20 and 35 regions | – | DNA methylation changes at birth might predict future asthma risk | ||
| Forno et al. [28] | Atopy (positive IgE to 1/5 aeroallergens) | 312 cases vs. 171 controls (age 9–20, EVA-PR) | Nasal brushes/cross-sectional | 8664 CpGs, top CpGs associated with epithelial barrier function |
72 African American children [29], 432 Dutch children (PIAMA), subset with CD326 positive epithelial cells 28/30 of top CpGs replicated, |
Replication across different ethnicities 1570 genes with expression changes and diff. methylation |
| Atopic asthma (doctor diagnosis and recent wheezing) | 169 cases vs. 104 controls (age 9–20, EVA-PR) | 28/30 of top CpGs replicated | ||||
| Cardenas et al. [30] | Asthma (doctor diagnosis and recent asthma episode or medication) | 65 cases vs. 463 controls at age 13 | Nasal swabs/cross-sectional |
Asthma 285 CpGs Allergic asthma 1235 CpGs FeNO 8372 CpGs Medication 130 CpGs |
Data comparison with two published cohorts (Inner city cohort [29], EVA-PR cohort [31]) 50–60% of CpGs replicated |
CpGs and DMRs annotated to Th2 activation and eosinophils and some previously associated with Asthma or IgE |
| Nicodemus-Johnson et al. [32] | Asthma (doctor diagnosis and recent asthma medication) | 74 cases vs. 41 controls (average age 40 years) | Cultured endobronchial epithelial cells | 40,893 CpGs including CpGs in ORMDL3 | – | Enrichment of mQTLs in genes with diff. methylation or asthma related genetic risk factors |