Table 4.

Top ACHS-II Dioxin-associated CpGs, selected by Bonferroni p≤6.74E-08.

ProbeID	Gene Symbol(s)	Coordinate	Exposure^a	% Differential Methylation (Mean ± SEM)^b	p-value^c	Exposure Regression Coefficient^c	Dioxin/Furan/PCB Association^d
cg00999904	ALLC	chr2:3704751	PCDDs	−4.64 ± 0.21	1.05E-09	−1.8964	TCDD
cg11354991	BBS4, HIGD2B	chr15:72978685	PCDDs	0.09 ± 0.01	6.04E-09	0.8172	TCDD, PCB52, PCB180
cg03510117	CYCS	chr7:25164991	PCDDs	0.37 ± 0.01	3.01E-08	0.6423	TCDD, PCB153
cg06169091	IGSF21	chr1:18678286	PCDDs	−2.49 ± 0.16	3.08E-08	−0.5569
cg21401636	KIF5C^e	chr2:149629217	PCDDs	−3.73 ± 0.30	1.88E-08	−0.6405	TCDD
cg03459668	RAB11FIP3	chr16:545622	PCDDs	−2.86 ± 0.14	2.26E-08	−0.4876	TCDD, PCB126
cg07303330	TAAR2	chr6:132945515	PCDDs	−0.88 ± 0.06	7.85E-09	−0.9439
cg26787894	CD83	chr6:14117621	PCDFs	0.29 ± 0.02	3.39E-08	0.4943	TCDD
cg06242879	ERBB3, PA2G4	chr12:56497745	PCDFs	0.36 ± 0.04	6.13E-09	0.3756	TCDD, PCB77
cg23269663	BCL3	chr19:45250480	cPCBs	−0.51 ± 0.03	5.15E-08	−0.2829	TCDD

CpGs are listed in order of exposure category and gene symbol. Individual exposures with ≥60% participants below the limit of detection

were excluded from the exposure groups with the exception of the ΣDioxins.

Exposure groups: ΣDioxins = sum of 28 dioxin and dioxin-like compounds, PCDDs = polychlorinated dibenzodioxins (n=7), PCDFs = polychlorinated dibenzofurans (n= 5), cPCBs = non-ortho subsituted PCBs (n=2), mPCBs = mono-ortho substituted PCBs (n=7).

Differential methylation was calculated by subtracting methylation in lowest exposure quartile from the highest.

Robust linear regression models were adjusted for age, race, sex, smoking status, bisulfite-conversion batch, and estimated percentages of CD4+ and CD8+ T-cells, CD19+ B-cells, monocytes, granulocytes, and natural killer cells.

Genes associated with dioxin, furan, or PCB exposure based on the 2019 Comparative Toxicogenomics Database.

Effect modification by race was detected. See Results 3.6 and Supplemental Table 3 for details.