Table 2.

CpGs associated with ${\log }_2\text{-transformed}$ urinary arsenic ($\text{false discovery rate \hspace{0.17em}}\left(\text{FDR}\right)<0.05$) discovered in HEALS (EPIC array).

							HEALS (discovery, EPIC)				BESTd (validation 450 K)
Name	Chr	Position	CpG Location	Nearest gene	Feature	Distance (basepairs)	Mean (SD)a	${\mathrm{\beta }}_{\text{sva}}$b	$p_{\text{sva}}$	$p_{\text{cell adjusted}}$c	Mean (SD)a	${\mathrm{\beta }}_{\text{sva}}$b	$p_{\text{sva}}$
cg01912040	17	1106553	Shore	ABR	Upstream	15,937	0.73 (0.05)	$-0.013$	$4.2\times {10}^{-13}$	$4.0\times {10}^{-9}$	0.72 (0.06)	$-0.008$	$2.8\times {10}^{-6}$
cg05962511	10	102730022	Shore	SEMA4G	Body	732	0.35 (0.05)	$-0.011$	$2.8\times {10}^{-12}$	$3.9\times {10}^{-8}$	0.34 (0.05)	$-0.004$	$6.6\times {10}^{-4}$
cg10003262	17	1106589	Shore	ABR	Upstream	15,973	0.34 (0.06)	$-0.014$	$2.4\times {10}^{-11}$	$6.3\times {10}^{-9}$	0.26 (0.05)	$-0.007$	$4.9\times {10}^{-6}$
cg17420142	18	32702783	Non-CpG island	MAPRE2	Body	81,169	0.59 (0.05)	$-0.011$	$3.1\times {10}^{-10}$	$1.7\times {10}^{-6}$	—	—	—
cg06466147	1	155188982	Non-CpG island	GBAP1	Body	19,459	0.62 (0.07)	$-0.016$	$6.2\times {10}^{-9}$	$2.0\times {10}^{-9}$	—	—	—
cg09082427	9	140349184	Shore	NSMF	Body	4,602	0.75 (0.05)	$-0.007$	$9.9\times {10}^{-9}$	$4.3\times {10}^{-6}$	—	—	—
cg04193083	17	41323562	Shore	NBR1	5'UTR	316	0.04 (0.02)	0.002	$3.3\times {10}^{-8}$	$7.0\times {10}^{-1}$	0.03 (0.01)	0.000	$4.1\times {10}^{-1}$
cg19534475	3	141632139	Non-CpG island	ATP1B3	Body	36,669	0.47 (0.04)	0.008	$9.6\times {10}^{-8}$	$4.6\times {10}^{-8}$	—	—	—
cg12608784	9	140349197	Shore	NSMF	Body	4,589	0.69 (0.05)	$-0.007$	$1.2\times {10}^{-7}$	$2.3\times {10}^{-5}$	—	—	—
cg14891900	17	76341204	Shelf	SOCS3	Downstream	14,954	0.91 (0.01)	0.003	$1.3\times {10}^{-7}$	$1.8\times {10}^{-7}$	0.93 (0.01)	$-0.001$	$3.2\times {10}^{-3}$
cg11308227	17	79202435	Non-CpG island	ENTHD2	3'UTR	10,456	0.54 (0.06)	$-0.011$	$1.3\times {10}^{-7}$	$1.6\times {10}^{-6}$	—	—	—
cg13832772	4	186283800	Non-CpG island	SNX25	Body	41,913	0.87 (0.03)	$-0.005$	$1.7\times {10}^{-7}$	$1.4\times {10}^{-2}$	0.94 (0.02)	0.000	$6.2\times {10}^{-1}$
cg15108641	10	99263320	Shelf	UBTD1	Body	4,552	0.35 (0.06)	0.008	$2.5\times {10}^{-7}$	$2.8\times {10}^{-5}$	—	—	—
cg09658504	9	140349188	Shore	NSMF	Body	4,598	0.47 (0.04)	$-0.005$	$3.0\times {10}^{-7}$	$7.4\times {10}^{-4}$	—	—	—
cg05438461	15	40401720	Shore	BMF	Promoter	632	0.20 (0.03)	0.005	$3.5\times {10}^{-7}$	$2.4\times {10}^{-5}$	—	—	—
cg10663081	20	36837543	Non-CpG island	KIAA1755	Downstream	51,631	0.47 (0.03)	$-0.004$	$3.7\times {10}^{-7}$	$1.5\times {10}^{-5}$	—	—	—
cg08759026	11	69061454	Non-CpG island	MYEOV	Promoter	159	0.24 (0.04)	$-0.004$	$6.7\times {10}^{-7}$	$4.8\times {10}^{-6}$	0.27 (0.04)	$-0.003$	$7.7\times {10}^{-5}$
cg11644394	7	144148615	Non-CpG island	TPK1	Downstream	419	0.62 (0.06)	0.008	$7.5\times {10}^{-7}$	$5.3\times {10}^{-4}$	—	—	—
cg05428706	10	102730130	Shore	SEMA4G	Body	840	0.79 (0.04)	$-0.008$	$8.2\times {10}^{-7}$	$1.8\times {10}^{-5}$	0.76 (0.04)	$-0.005$	$1.3\times {10}^{-4}$
cg12865207	3	138669373	Shore	FOXL2NB	Body	3,297	0.15 (0.03)	0.004	$1.0\times {10}^{-6}$	$3.4\times {10}^{-3}$	—	—	—
cg09183146	16	1429863	Island	UNKL	Promoter	34,842	0.26 (0.05)	$-0.01$	$1.2\times {10}^{-6}$	$3.4\times {10}^{-6}$	0.24 (0.05)	$-0.007$	$2.4\times {10}^{-5}$
cg04622454	9	140349128	Shore	NELF	Body	4,658	0.63 (0.04)	$-0.005$	$1.3\times {10}^{-6}$	$6.1\times {10}^{-3}$	0.57 (0.04)	$-0.003$	$1.1\times {10}^{-3}$
cg06381803	19	46119475	Island	EML2	Body	29,300	0.41 (0.07)	$-0.012$	$1.4\times {10}^{-6}$	$8.8\times {10}^{-6}$	0.40 (0.07)	$-0.009$	$7.9\times {10}^{-6}$
cg02772605	1	28912323	Shelf	SNHG12	Upstream	3957	0.88 (0.02)	0.003	$1.4\times {10}^{-6}$	$2.7\times {10}^{-6}$	0.89 (0.02)	0.000	$9.4\times {10}^{-1}$
cg10283165	19	17375666	Non-CpG island	USHBP1	Promoter	61	0.39 (0.05)	$-0.006$	$1.4\times {10}^{-6}$	$1.3\times {10}^{-3}$	—	—	—
cg04891961	17	27939900	Island	ANKRD13B	Body	19,373	0.49 (0.07)	$-0.009$	$1.4\times {10}^{-6}$	$1.6\times {10}^{-5}$	0.47 (0.08)	0.002	$1.8\times {10}^{-1}$
cg12746706	6	169276508	Non-CpG island	SMOC2	Upstream	207,834	0.86 (0.03)	$-0.005$	$1.5\times {10}^{-6}$	$8.2\times {10}^{-3}$	0.94 (0.01)	$-0.001$	$1.3\times {10}^{-1}$
cg02330195	10	73342047	Non-CpG island	CDH23	Body	142,463	0.67 (0.04)	0.005	$1.5\times {10}^{-6}$	$3.7\times {10}^{-3}$	—	—	—
cg08077890	18	157838	Shore	USP14	Promoter	645	0.77 (0.04)	0.006	$1.6\times {10}^{-6}$	$1.4\times {10}^{-3}$	—	—	—
cg20433952	17	55607898	Non-CpG island	MSI2	Body	273,524	0.51 (0.04)	$-0.008$	$1.9\times {10}^{-6}$	$4.4\times {10}^{-3}$	0.52 (0.04)	$-0.003$	$3.4\times {10}^{-2}$
cg10185759	12	60366859	Non-CpG island	SLC16A7	Downstream	283,741	0.46 (0.04)	$-0.007$	$1.9\times {10}^{-6}$	$1.3\times {10}^{-7}$	—	—	—
cg05646745	10	135172466	Shore	FUOM	Promoter	937	0.73 (0.04)	0.005	$1.9\times {10}^{-6}$	$4.0\times {10}^{-7}$	—	—	—
cg22345623	9	125050297	Non-CpG island	MRRF	Body	17,154	0.78 (0.05)	$-0.007$	$2.0\times {10}^{-6}$	$2.3\times {10}^{-7}$	—	—	—
cg13480898	19	10195914	Shore	C19orf66	Promoter	892	0.73 (0.05)	$-0.005$	$2.0\times {10}^{-6}$	$2.8\times {10}^{-7}$	0.76 (0.04)	$-0.007$	$3.7\times {10}^{-8}$

Note: Results from the discovery analysis are shown for CpGs associated with ${\log }_2\text{-transformed}$ urinary arsenic (creatinine adjusted) below false discovery rate (FDR) of 0.05 from models adjusted for age, sex, BMI category, smoking status, and 27 SVs. The p-values are obtained from the analyses using methylation expressed as M-values as the outcome variable, and reported association estimates (${\mathrm{\beta }}_{\text{sva}}$) are from analysis with methylation expressed as beta values as the outcome variable (for easier interpretability). Gene assignments are from UCSC gene annotation provided by Illumina. The replication results from BEST are also presented for the CpGs measured on both the EPIC and $450\mathrm{K}$ arrays. Extended results for arsenic-associated CpGs with $p<0.05$ are presented in Excel Table S1. —, no data; BEST, Bangladesh Vitamin E and Selenium Trial; BMI, body mass index; Chr, chromosome; HEALS, Health Effects of Arsenic Longitudinal Study; SD, standard deviation; SV, surrogate variable.

^aMean and SD of beta values at each CpG (range: 0 to 1) in HEALS and BEST.

^b${\mathrm{\beta }}_{\text{sva}}$ and $p_{\text{sva}}$ are association estimate and p-value from covariate and SV-adjusted analysis model.

^c$p_{\text{cell adjusted}}$ is p-value from the analysis model of ${\log }_2\text{-transformed}$ urinary arsenic and adjusted for covariates and estimated cell type proportions.

^dResults from the replication analysis in BEST are shown for ${\log }_2\text{-transformed}$ urinary arsenic–CpG associations from models adjusted for age, sex, BMI category, smoking status, and 24 SVs.