Table 3.

Results from gene set enrichment analysis of hallmark gene set collection ($n=54$ sets) among the urinary arsenic–associated CpGs identified in the HEALS discovery analysis ($n=396$) and meta-analysis of HEALS and BEST ($n=796$).

		Top 500 arsenic-associated CpGsa		Arsenic-associated CpGs below $\text{FDR}<0.05$b
	n	Genes	p	Genes	p
HEALS
Angiogenesis	36	3	$6.4\times {10}^{-3}$	—	—
Cholesterol homeostasis	74	4	$1.2\times {10}^{-2}$	—	—
$\text{TNF}\mathrm{\alpha }$ signaling via $\text{NF}\mathrm{\kappa }\mathrm{B}$	200	7	$2.1\times {10}^{-2}$	—	—
META-ANALYSIS
Allograft rejection	200	9	$2.2\times {10}^{-3}$	4	$1.9\times {10}^{-2}$
${\text{PI}}_3\mathrm{K}/\text{AKT}/\text{mTOR}$	105	6	$9.8\times {10}^{-3}$	3	$2.2\times {10}^{-2}$
Reactive oxygen species pathway	49	3	$1.4\times {10}^{-2}$	2	$9.1\times {10}^{-3}$
Inflammatory response	200	6	$2.9\times {10}^{-2}$	3	$4.4\times {10}^{-2}$
$\text{TNF}\mathrm{\alpha }$ signaling via $\text{NF}\mathrm{\kappa }\mathrm{B}$	200	7	$4.1\times {10}^{-2}$	4	$3.1\times {10}^{-2}$
Estrogen response early	200	10	$1.1\times {10}^{-2}$	—	—
UV response up-regulated	158	7	$1.4\times {10}^{-2}$	—	—
MTORC1 signaling	200	—	—	4	$1.8\times {10}^{-2}$
Oxidative phosphorylation	200	—	—	3	$3.1\times {10}^{-2}$
MYC targets V1	200	—	—	3	$4.7\times {10}^{-2}$
Apical junction	200	—	—	4	$4.8\times {10}^{-2}$

Note: Gene annotations for arsenic-associated CpGs are provided as gene set input for the gometh function. Results are presented for hallmark gene sets ($n=54$ sets) with at least two genes from arsenic-associated CpG gene set and enrichment ($p<0.05$). Background gene set for $450\mathrm{K}$ is 19,246 genes, and EPIC is 23,234 genes. The table reports total number of genes in set (n), genes identified in pathway from CpG gene set, and p-value from CpG bias-corrected hypergeometric test. —, no data; BEST, Bangladesh Vitamin E and Selenium Trial; FDR, false discovery rate; HEALS, Health Effects of Arsenic Longitudinal Study; $\text{TNF}\mathrm{\alpha }$, tumor necrosis factor $\mathrm{\alpha }$.

^aTop 500 arsenic-associated CpGs, annotated to 348 unique genes in the HEALS discovery analysis (EPIC array), 338 unique genes in the meta-analysis ($450\mathrm{K}$ array).

^bArsenic-associated CpGs ($\text{FDR}<0.05$), annotated to 21 unique genes in the discovery analysis, 153 unique genes in the meta-analysis.