Table 3.

EWIS of DNA methylation and BMI change on adult-onset asthma: enrichment test results for 17 inflammation pathways and NLRP3-IL1B-IL17 axis.

Pathway	#Genes	#CpGs	Enrichment p-Value
			Basic Model	Adjusted for Physical Activity	Unadjusted for Neutrophil Counts
Adhesion-extravasation-migration	142	1737	0.67	0.60	0.39
Apoptosis signaling	68	1210	0.50	0.37	0.22
Calcium signaling	14	413	0.29	0.34	0.21
Complement cascade	40	483	0.45	0.64	0.34
Cytokine signaling	172	1883	0.26	0.35	0.21
Eicosanoid signaling	39	450	0.48	0.17	0.61
Glucocorticoid/PPAR signaling	21	404	0.063	0.15	0.072
G-Protein coupled receptor signaling	42	1133	0.47	0.88	0.46
Innate pathogen detection	50	515	0.059	0.12	0.13
Leukocyte signaling	121	1429	0.35	0.49	0.34
MAPK signaling	118	2682	0.13	0.33	0.24
Natural killer cell signaling	31	368	0.91	0.75	0.91
NF-κB signaling	33	654	0.70	0.49	0.62
Phagocytosis-Ag presentation	39	1058	0.51	0.89	0.71
PI3K/AKT signaling	37	907	0.98	0.98	0.89
ROS/glutathione/cytotoxic granules	22	190	0.24	0.55	0.14
TNF superfamily signaling	38	537	0.085	0.33	0.065
Global inflammation §	1027	15985	0.048	0.23	0.028
NLRP3-IL1B-IL17 axis	11	219	0.046	0.13	0.15

The basic model regressed adult-onset asthma on BMI change, residuals of DNA methylation at a single CpG site, and their multiplicative interaction upon adjustment for BMI at SAPALDIA2, age, sex, education level, study area, pack-years of cigarettes smoked in life, bench time, and white blood cell composition estimates for B cells, CD4 T cells, CD8 T cells, natural killer cells, monocytes, and eosinophils. ^§ Total of the 17 inflammation pathways; the number of CpG in this pathway (15,985) is smaller than the sum of the CpGs assigned to 17 pathways because there are CpGs assigned to multiple pathways, although the 17 pathways are mutually exclusive at gene level. Enrichment p-values are in bold if p < 0.05.