Table 2.
Associations among comethylation modules, transcriptional pathways, and clinical measures
| Variables | WGCNA comethylation modules (No. of DMCs) | ||||||
|---|---|---|---|---|---|---|---|
| NMA associated | MA associated | ||||||
| Orange | Green | Black | Blue | Red | Turquoise | Yellow | |
| (31) | (35) | (15) | (74) | (17) | (73) | (24) | |
| Correlated genes and pathways | |||||||
| No. of correlated genes | 2,217 | 2,511 | 3,752 | 2,825 | 1,721 | 1,133 | 2,351 |
| No. of unique genes | 115 | 110 | 794 | 234 | 46 | 85 | 391 |
| No. of pathways | 0 | 0 | 11 | 0 | 0 | 36 | 33 |
| No. of hub DMCs | 0 | 4 | 9 | 8 | 7 | 19 | 9 |
| First pathway | — | — | Gene expression | — | — | S. aureus infection | Eukaryotic translation elongation |
| Second pathway | — | — | T cell receptor signaling pathway | — | — | Rheumatoid arthritis | Cytoplasmic ribosomal proteins |
| Third pathway | — | — | Cancer immunotherapy by PD-1 blockade | — | — | Tuberculosis | Peptide chain elongation |
| Clinical measures | |||||||
| Asthma severity (n = 142) |
5.81
4.1 × 10−8 |
−6.02
1.5 × 10−8 |
−5.20
6.9 × 10−7 |
−5.69
7.4 × 10−8 |
4.72
5.6 × 10−6 |
−5.24
6.0 × 10−7 |
4.60
9.6 × 10−6 |
| FEV1% predicted (n = 142) |
−0.36
1.2 × 10−5 |
0.38
3.4 × 10−6 |
0.40
7.6 × 10−7 |
0.40
6.7 × 10−7 |
−0.37
7.8 × 10−6 |
0.38
3.4 × 10−6 |
−0.33
5.1 × 10−5 |
| FEV1/FVC (n = 142) |
−0.29
5.2 × 10−4 |
0.29
4.0 × 10−4 |
0.26
2.2 × 10−3 |
0.20 0.018 |
−0.21 0.013 |
0.25
2.6 × 10−3 |
ns |
| Total serum IgE (n = 141) |
0.21 0.013 |
−0.23 6.9 × 10−3 |
−0.30
2.8 × 10−4 |
−0.31
1.7 × 10−4 |
0.26
1.8 × 10−3 |
−0.21 0.011 |
0.29
4.53 × 10−4 |
| FeNO (n = 135) |
0.18 0.037 |
ns |
−0.27
2.9 × 10−3 |
−0.22
9.7 × 10−3 |
0.26
2.0 × 10−3 |
ns |
0.28
9.4 × 10−4 |
| BAL eosinophilia (n = 140) |
0.22 8.7x10−3 |
ns |
−0.24
4.5 × 10−3 |
−0.26
2.1 × 10−3 |
0.24
4.6 × 10−3 |
−0.17 0.039 |
0.30
3.5 × 10−4 |
| BAL neutrophilia (n = 140) |
ns | ns | ns | ns | ns | ns | ns |
| Blood eosinophilia (n = 141) |
ns | ns | ns | ns | ns | ns | ns |
| BMI (n = 142) |
0.26
1.9 × 10−3 |
ns | ns | ns | ns | ns |
0.24
3.5 × 10−3 |
Of the 69 NMA-DMCs and the 554 MA-DMCs, 66 (95.65%) and 203 (36.64%) formed two and five comethylation modules, respectively (15 to 74 CpGs in each module). See SI Appendix, Figs. S4 and S5 for cluster dendrograms of the seven modules. Correlated genes and pathways: For each module, the number of correlated genes (FDR < 0.10), the number of uniquely correlated genes (FDR < 0.10 only in that module), the number of hub DMCs, and the top three enriched pathways for the uniquely correlated genes are shown. SI Appendix, Table S3 lists all the pathway enrichments in each module. Clinical measures: Correlation coefficients and P values are shown between clinical measures and module eigenvectors. Significant P values after Bonferroni-correcting for nine clinical phenotypes (P < 5.56 × 10−3) are shown in bold. The numbers of subjects with measurements for each variable are shown. Asthma severity is determined by STEP classification (18). ns, not significant (P > 0.05).