Table 2.

Top ten CpGs independently associated with source-specific transportation noise and air pollution in the SAPALDIA study, multiexposure models.

Exposure	CpG ID	CHR	Location	Gene	Feature	Model 1	SE	$p$-Value	P (FDR)	Model 2	SE	$p$-Value
						Beta				Beta
Aircraft Lden	cg02286155	5	176826262	NA	NA	$-0.007$	0.001	$1.48\times {10}^{-6}$	0.637	$-0.007$	0.001	$2.13\times {10}^{-6}$
	cg15063530	2	17716941	NA	NA	$-0.009$	0.002	$8.14\times {10}^{-6}$	0.659	$-0.009$	0.002	$8.14\times {10}^{-6}$
	cg16218477	7	1066167	C7orf50	Body	$-0.004$	0.001	$8.53\times {10}^{-6}$	0.659	$-0.004$	0.001	$7.05\times {10}^{-6}$
	cg21602842	18	46291908	KIAA0427	Body	$-0.005$	0.001	$9.84\times {10}^{-6}$	0.659	$-0.005$	0.001	$9.84\times {10}^{-6}$
	cg09042449	10	44064225	ZNF239	5′UTR	$-0.002$	0.0004	$1.06\times {10}^{-5}$	0.659	$-0.002$	0.0004	$1.18\times {10}^{-5}$
	cg10975000a	13	28371375	NA	NA	$-0.002$	0.0005	$1.12\times {10}^{-5}$	0.659	$-0.002$	0.0005	$1.16\times {10}^{-5}$
	cg06220958	17	10452851	MYH2	5′UTR	0.011	0.002	$1.24\times {10}^{-5}$	0.659	0.010	0.002	$1.43\times {10}^{-5}$
	cg25462190a	5	177547067	N4BP3	Body	$-0.007$	0.002	$1.32\times {10}^{-5}$	0.659	$-0.007$	0.002	$1.06\times {10}^{-5}$
	cg11944797	13	99135711	STK24	Body	$-0.001$	0.0003	$1.38\times {10}^{-5}$	0.659	$-0.001$	0.0003	$1.70\times {10}^{-5}$
	cg04635504	11	2829241	KCNQ1	Body	$-0.005$	0.001	$1.61\times {10}^{-5}$	0.664	$-0.005$	0.001	$1.62\times {10}^{-5}$
Railway Lden	cg25201280a	15	35838552	ATPBD4	TSS200	$-0.001$	0.0002	$1.74\times {10}^{-7}$	0.075	$-0.001$	0.0002	$1.99\times {10}^{-7}$
	cg24653263a	5	38258335	EGFLAM	TSS200	$-0.003$	0.001	$8.97\times {10}^{-7}$	0.193	$-0.003$	0.001	$1.01\times {10}^{-6}$
	cg16825060a	8	144242342	LY6H	TSS1500	$-0.003$	0.001	$2.34\times {10}^{-6}$	0.256	$-0.003$	0.001	$2.56\times {10}^{-6}$
	cg23468045	5	12669584	NA	NA	0.001	0.0002	$2.37\times {10}^{-6}$	0.256	0.001	0.0002	$2.19\times {10}^{-6}$
	cg19270309a	17	77712853	ENPP7	3′UTR	0.002	0.0005	$3.25\times {10}^{-6}$	0.266	0.002	0.0005	$3.56\times {10}^{-6}$
	cg07461273	7	99697172	MCM7	Body	$-0.004$	0.001	$3.78\times {10}^{-6}$	0.266	$-0.004$	0.001	$3.70\times {10}^{-6}$
	cg01301319	7	27153580	HOXA3	5′UTR	$-0.003$	0.001	$4.60\times {10}^{-6}$	0.266	$-0.003$	0.001	$4.32\times {10}^{-6}$
	cg23113715a	22	25800663	NA	NA	$-0.004$	0.001	$5.79\times {10}^{-6}$	0.266	$-0.004$	0.001	$5.73\times {10}^{-6}$
	cg13402217	1	151584375	SNX27	TSS1500	$-0.003$	0.001	$6.03\times {10}^{-6}$	0.266	$-0.003$	0.001	$5.50\times {10}^{-6}$
	cg24047259a	14	65347275	NA	NA	$-0.001$	0.0003	$7.35\times {10}^{-6}$	0.266	$-0.001$	0.0003	$4.90\times {10}^{-6}$
Road traffic Lden	cg09129334	13	111837676	ARHGEF7	Body	$-0.007$	0.001	$1.73\times {10}^{-6}$	0.384	$-0.007$	0.001	$2.12\times {10}^{-6}$
	cg17383236a	7	100167504	NA	NA	$-0.002$	0.0005	$2.76\times {10}^{-6}$	0.384	$-0.002$	0.0005	$2.74\times {10}^{-6}$
	cg01066220	6	31696240	DDAH2	Body	0.001	0.0001	$3.48\times {10}^{-6}$	0.384	0.001	0.0001	$4.29\times {10}^{-6}$
	cg23910243a	16	31484618	TGFB1I1	Body	$-0.002$	0.0005	$4.32\times {10}^{-6}$	0.384	$-0.002$	0.0005	$7.13\times {10}^{-6}$
	cg06646021a	1	229406520	RAB4A	TSS1500	$-0.005$	0.001	$4.47\times {10}^{-6}$	0.384	$-0.005$	0.001	$4.78\times {10}^{-6}$
	cg03066594	20	10415919	C20orf94	TSS200	0.0005	0.0001	$6.00\times {10}^{-6}$	0.386	0.0004	0.0001	$7.82\times {10}^{-6}$
	cg03966094a	22	21058792	TMEM191A	Body	$-0.003$	0.001	$7.06\times {10}^{-6}$	0.386	$-0.003$	0.001	$6.73\times {10}^{-6}$
	cg13948857	5	131763756	C5orf56	Body	$-0.003$	0.001	$7.17\times {10}^{-6}$	0.386	$-0.003$	0.001	$7.22\times {10}^{-6}$
	cg08351004a	2	172965650	DLX2	Body	$-0.002$	0.0005	$9.53\times {10}^{-6}$	0.456	$-0.002$	0.0005	$1.23\times {10}^{-5}$
	cg13777730	1	234793300	NA	NA	$-0.003$	0.001	$1.07\times {10}^{-5}$	0.458	$-0.003$	0.001	$1.10\times {10}^{-5}$
${\mathrm{NO}}_2$	cg04337651a	2	239344738	ASB1	Body	0.004	0.001	$2.06\times {10}^{-6}$	0.657	0.003	0.001	$2.67\times {10}^{-6}$
	cg18776472	10	50732819	ERCC6	Body	$-0.001$	0.0002	$8.20\times {10}^{-6}$	0.657	$-0.001$	0.0002	$1.00\times {10}^{-5}$
	cg18601596	6	39283313	KCNK16	Body	0.006	0.001	$8.21\times {10}^{-6}$	0.657	0.006	0.001	$8.62\times {10}^{-6}$
	cg12392998	17	79550668	NPLOC4	Body	$-0.002$	0.0004	$8.72\times {10}^{-6}$	0.657	$-0.002$	0.0004	$1.04\times {10}^{-5}$
	cg16550606	13	50160670	RCBTB1	TSS1500	0.004	0.001	$1.33\times {10}^{-5}$	0.657	0.004	0.001	$1.44\times {10}^{-5}$
	cg25266109	19	12404608	ZNF44	Body	$-0.0004$	0.0001	$1.38\times {10}^{-5}$	0.657	$-0.0004$	0.0001	$1.20\times {10}^{-5}$
	cg01746514a	14	24520922	LRRC16B	TSS1500	$-0.001$	0.0002	$1.43\times {10}^{-5}$	0.657	$-0.001$	0.0002	$1.58\times {10}^{-5}$
	cg15811902	15	75918385	SNUPN	5′UTR	$-0.002$	0.0005	$1.61\times {10}^{-5}$	0.657	$-0.002$	0.0005	$1.48\times {10}^{-5}$
	cg26898336a	17	15244519	TEKT3	5′UTR	0.002	0.0005	$1.65\times {10}^{-5}$	0.657	0.002	0.0005	$1.89\times {10}^{-5}$
	cg21099332	5	39270715	NA	NA	0.004	0.001	$1.66\times {10}^{-5}$	0.657	0.004	0.001	$1.88\times {10}^{-5}$
${\mathrm{PM}}_{2.5}$	cg26704043	6	5282702	FARS2	5′UTR	0.014	0.003	$4.18\times {10}^{-7}$	0.180	0.014	0.003	$6.22\times {10}^{-7}$
	cg05157625	14	93153553	RIN3	Body	0.021	0.004	$1.08\times {10}^{-6}$	0.231	0.021	0.004	${1.13\times 10}^{-6}$
	cg20099458a	7	5272275	WIPI2	3′UTR	0.014	0.003	$1.61\times {10}^{-6}$	0.231	0.014	0.003	$1.58\times {10}^{-6}$
	cg06587257	12	50452135	ACCN2	5′UTR	0.022	0.005	$2.71\times {10}^{-6}$	0.292	0.023	0.005	$2.04\times {10}^{-6}$
	cg14531665	9	91058614	SPIN1	Body	0.012	0.003	$5.91\times {10}^{-6}$	0.398	0.011	0.003	$7.07\times {10}^{-6}$
	cg06526020	6	34308880	NUDT3	Body	0.029	0.006	$6.43\times {10}^{-6}$	0.398	0.028	0.006	$8.80\times {10}^{-6}$
	cg21058520	6	100914733	NA	NA	0.004	0.001	$6.76\times {10}^{-6}$	0.398	0.004	0.001	$8.31\times {10}^{-6}$
	cg16259904	10	134146220	LRRC27	5′UTR	0.027	0.006	$8.90\times {10}^{-6}$	0.398	0.027	0.006	$1.01\times {10}^{-5}$
	cg12770741	17	883776	NXN	TSS1500	0.018	0.004	$9.15\times {10}^{-6}$	0.398	0.018	0.004	$1.01\times {10}^{-5}$
	cg26750893a	2	38043481	NA	NA	0.016	0.004	$1.05\times {10}^{-5}$	0.398	0.016	0.004	$1.28\times {10}^{-5}$

Note: Beta coefficients represent increase or decrease in DNA methylation per $10\mathrm{\hspace{0.17em}dB}$ increase in aircraft, railway or road traffic Lden or 10 $\mathrm{\mu }\mathrm{g}/{\mathrm{m}}^3$ increase in ${\mathrm{NO}}_2$ or ${\mathrm{PM}}_{2.5}$. All estimates were from multiexposure epigenome-wide linear mixed-effects models, with random intercept at the level of participant. Multiexposure models included all five exposures (aircraft, railway, road traffic Lden and respective truncation indicators, ${\mathrm{NO}}_2$ and ${\mathrm{PM}}_{2.5}$) at the same time. In a preliminary step, DNA methylation $\mathrm{\beta }$-values were regressed on the Illumina control probe-derived first 30 principal components to correct for correlation structures and technical bias, and residuals of these regressions covering 430,477 CpGs were used as the technical bias-corrected methylation level at the CpG sites. Extreme values of the residuals (lying beyond three times the interquartile range below the first quartile and above the third quartile at each CpG site) were replaced with their corresponding detection threshold value (“modified winsorization”). The “winsorized” data were then used as the dependent variables in the EWAS. Model 1: adjusted for age; sex; educational level; area; neighborhood socioeconomic status; greenness index; smoking status; smoking pack-years; exposure to passive smoke; consumption of fruits, vegetables and alcohol; nested study; asthma status; noise truncation indicators; survey; and leukocyte composition (main model). Model 2: Model $1+\text{body}$ mass index and physical activity. CHR, chromosome; CpG, Cytosine-phosphate-Guanine; Lden, day-evening-night noise level; NA, not annotated; ${\mathrm{NO}}_2$, particulate matter with aerodynamic diameter $<2.5\mathrm{\mu }\mathrm{m}$; SAPALDIA, Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults; SE, standard error.

^aLocation overlaps with significant differentially methylated region.