Table 3.

Differentially methylated CpGs at a family-wise error rate ($p<9\times {10}^{-8}$) in relation to use of active ingredients, Agricultural Lung Health Study, 2009–2013.

Active ingredient	Probe	Chr	Positiona	Users ($n$)b	Never users ($n$)	Beta	SE	$p$-Valuec	Gene name [symbol (full name)]d
Herbicide
Dicamba	cg08004045	3	127797258	43	424	0.008	0.001	1.05 $\times {10}^{–10}$	RUVBL1-AS1 (RuvB Like AAA ATPase 1 antisense RNA 1)
	cg14830371	8	25991602	43	423	$-0.006$	0.001	1.62 $\times {10}^{–9}$	EBF2 (early B cell factor transcription factor 2)
	cg23238147	1	15439013	43	424	$-0.006$	0.001	2.17 $\times {10}^{–8}$	TMEM51-AS1 (transmembrane protein 51 antisense RNA 1)
Picloram	cg06216309	7	101603359	32	976	0.029	0.004	9.27 $\times {10}^{–12}$	CUX1 (cut like homeobox 1)
	cg04852443	1	2990064	32	974	$-0.004$	0.001	5.16 $\times {10}^{–10}$	PRDM16 (PR domain containing 16)
	cg09671989	16	88330828	32	976	0.006	0.001	7.15 $\times {10}^{–9}$	LINC02182 (long intergenic non-protein coding RNA 2182)
	cg21760990	6	121656542	32	979	0.029	0.005	1.19 $\times {10}^{–8}$	TBC1D32 (TBC1 domain family member 32)
	cg04815626	8	9912509	32	979	$-0.001$	0.0003	1.44 $\times {10}^{–8}$	MSRA (methionine sulfoxide reductase A)
	cg16188532	13	47471090	32	979	$-0.001$	0.0002	5.76 $\times {10}^{–8}$	HTR2A (5-hydroxytryptamine receptor 2A)
	cg16273766	11	28131811	32	979	$-0.001$	0.0001	6.03 $\times {10}^{–8}$	METTL15 (methyltransferase-like 15)
	cg02034311	13	112547999	32	978	$-0.056$	0.010	7.10 $\times {10}^{–8}$	LINC00354 (long intergenic non-protein coding RNA 354)
Mesotrione	cg18025430	11	60048004	39	1,018	$-0.011$	0.002	5.04 $\times {10}^{–9}$	MS4A4A (membrane spanning 4-domains A4A)
	cg02156591	3	130480267	39	1,019	$-0.033$	0.006	8.86 $\times {10}^{–9}$	PIK3R4 (phosphoinositide-3-kinase regulatory subunit 4)
	cg01919701	13	112996346	39	1,020	0.051	0.009	1.12 $\times {10}^{–8}$	LINC01044 (long intergenic non-protein coding RNA 1044)
	cg22053500	6	111580379	39	1,017	$-0.002$	0.0003	1.25 $\times {10}^{–8}$	MFSD4B (major facilitator superfamily domain containing 4B)
	cg21270074	20	49412129	39	1,020	$-0.001$	0.0001	2.50 $\times {10}^{–8}$	BCAS4 (breast carcinoma amplified sequence 4)
	cg03584506	11	39689828	39	1,019	0.057	0.010	3.46 $\times {10}^{–8}$	LRRC4C (leucine rich repeat containing 4C)
	cg16258223	5	134377058	39	1,020	0.054	0.010	4.34 $\times {10}^{–8}$	C5orf66-AS1 (esophagus epithelial intergenic associated transcript)
	cg11223552	3	158984799	39	1,020	0.044	0.008	4.37 $\times {10}^{–8}$	SCHIP1 (schwannomin interacting protein 1)
	cg14870603	8	31986050	39	1,018	0.059	0.011	4.39 $\times {10}^{–8}$	NRG1-IT1 (neuregulin 1 intronic transcript 1)
	cg24255843	2	192140815	39	1,020	0.004	0.0007	5.22 $\times {10}^{–8}$	MYO1B (myosin IB)
	cg15263667	2	29118655	39	1,019	$-0.001$	0.0002	6.51 $\times {10}^{–8}$	WDR43 (WD repeat domain 43)
	cg09849314	3	195283427	38	1,018	$-0.067$	0.012	7.87 $\times {10}^{–8}$	PPP1R2 (protein phosphatase 1 regulatory inhibitor subunit 2)
Acetochlor	cg16722983	14	91244421	41	968	0.031	0.005	1.57 $\times {10}^{–9}$	TTC7B (tetratricopeptide repeat domain 7B)
	cg08165462	19	652493	41	968	0.013	0.002	1.47 $\times {10}^{–8}$	RNF126 (ring finger protein 126)
	cg01869283	7	37209906	40	964	0.009	0.002	1.77 $\times {10}^{–8}$	ELMO1-AS1 (engulfment and cell motility 1 antisense RNA 1)
	cg04108706	1	180126520	41	967	0.017	0.003	3.72 $\times {10}^{–8}$	QSOX1 (quiescin sulfhydryl oxidase 1)
	cg10252897	17	38275458	41	968	0.008	0.002	5.56 $\times {10}^{–8}$	MSL1 (male-specific lethal 1)
	cg00919585	3	51975770	41	968	$-0.002$	0.0004	7.90 $\times {10}^{–8}$	RRP9 (ribosomal RNA processing 9, U3 small nucleolar RNA binding protein)
Metolachlor	cg17001333	1	213843678	53	454	$-0.079$	0.014	5.31 $\times {10}^{–9}$	LINC00538 (long intergenic non-protein coding RNA 538)
	cg20390515	2	945697	53	454	$-0.002$	0.0003	9.07 $\times {10}^{–9}$	SNTG2 (syntrophin gamma 2)
	cg18085807	6	30313188	51	439	$-0.002$	0.0003	2.51 $\times {10}^{–8}$	RPP21 (ribonuclease P/MRP subunit p21)
	cg14219242	5	179051847	53	454	0.002	0.0004	4.06 $\times {10}^{–8}$	HNRNPH1 (heterogeneous nuclear ribonucleoprotein H1)
	cg16702144	9	131218309	52	448	0.0004	0.00007	8.18 $\times {10}^{–8}$	ODF2 (outer dense fiber of sperm tails 2)
Glyphosate	cg06950346	7	123978181	523	69	$-0.027$	0.005	1.21 $\times {10}^{–8}$	LOC101928211 (uncharacterized LOC101928211)
Atrazine	cg01867395	11	31839628	172	187	0.033	0.006	1.99 $\times {10}^{–8}$	PAX6 (paired box 6)
Insecticide
Heptachlor	cg18284070	14	57736207	242	889	$-0.0004$	0.00007	1.19 $\times {10}^{–8}$	EXOC5 (exocyst complex component 5)
	cg04265842	3	156807650	242	889	$-0.007$	0.001	5.40 $\times {10}^{–8}$	LINC00881 (long intergenic non-protein coding RNA 881)
	cg16310513	18	55471075	242	889	0.026	0.005	7.08 $\times {10}^{–8}$	ATP8B1 (ATPase phospholipid transporting 8B1)
Malathion	cg26210302	3	42913809	36	196	0.045	0.008	5.13 $\times {10}^{–9}$	CYP8B1 (cytochrome P450 family 8 subfamily B member 1)

Note: All significant findings at $\text{FDR}<0.05$ are shown in Excel Tables S2–S10. Chr, chromosome; CpGs, C-phosphate-G sites; FDR, false-discovery rate; SE, standard error.

^aBuild hg19/GRCh37.

^bExcept for heptachlor, users reported both past and current use of the pesticide. Heptachlor users only had past use.

^cAnalyses conducted using robust linear regression, adjusting for the selection factor (asthma status), age at blood collection, pack years, smoking (never, former, current), state of residence, and seven estimated cell types.

^dAnnotated using HOMER (version 4.10.3; Heinz et al. 2010).