Table 2 Differentially methylated regions (DMRs, Šidák p-value < 0.01) associated with asthma at 6 years among infants hospitalized for bronchiolitis (n = 506)

From: Epigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants

DMRs (chromosome:position)	Width (bp)	N of CpGs	Šidák p-value	Nearest genes	Model^a	Direction of effect^b	Overlap with promoter	Distance to TSS (bp)^c	Evidence for open chromatin^d	Statistically significant interaction by rhinovirus infection^e
chr1:19969931-19970337	407	10	1.61 × 10⁻⁵	NBL1	both	+	No	28	No	No
chr1:46668513-46668840	328	5	7.10 × 10⁻⁴	POMGNT1	LRT-2df	+	No	17,137	Yes	No
chr1:94057512-94057789	278	7	4.24 × 10⁻³	BCAR3-AS1	linear	-	Yes	0	Yes	n/a
chr1:247681297-247681766	470	6	4.27 × 10⁻³	GCSAML	linear	+	No	10,903	Yes	n/a
chr3:48632568-48633059	492	8	4.23 × 10⁻⁶	COL7A1	both	-	Yes	0	No	No
chr5:78365647-78365830	184	7	1.75 × 10⁻²	BHMT2	LRT-2df	-	No	100	No	No
chr5:135416029-135416613	585	9	2.76 × 10⁻⁵	VTRNA2-1	linear	-	Yes	0	Yes	n/a
chr6:26225246-26225407	162	7	1.97 × 10⁻⁵	HIST1H3E	linear	-	Yes	0	No	n/a
chr6:28058724-28058973	250	8	1.17 × 10⁻⁹	ZSCAN12P1	LRT-2df	-	No	139	Yes	Yes
chr6:28129313-28129656	344	9	8.32 × 10⁻⁵	ZKSCAN8P1	both	+	Yes	0	Yes	No
chr6:42927940-42928200	261	9	7.22 × 10⁻⁸	GNMT	both	-	Yes	−300	Yes	Yes
chr7:95025855-95026248	394	14	2.20 × 10⁻⁴	PON3	both	+	Yes	−168	Yes	No
chr7:150644459-150644866	408	5	1.10 × 10⁻³	KCNH2	both	+	No	8051	No	No
chr8:144631768-144631921	154	5	8.49 × 10⁻⁴	GSDMD	LRT-2df	+	No	−3636	Yes	Yes
chr10:131989303-131989849	547	6	7.38 × 10⁻⁶	GLRX3	linear	-	No	54,664	No	n/a
chr11:2890258-2890725	468	24	6.86 × 10⁻⁷	KCNQ1DN	linear	-	Yes	−538	No	n/a
chr11:2920052-2920414	363	7	1.52 × 10⁻³	SLC22A18AS	LRT-2df	+	No	4761	Yes	Yes
chr12:44152565-44152940	376	9	3.46 × 10⁻⁵	IRAK4; PUS7L	linear	+	Yes	0	Yes	n/a
chr13:114103452-114103796	345	7	2.41 × 10⁻⁵	ADPRHL1	both	-	Yes	0	Yes	No
chr15:23810334-23810861	528	7	1.59 × 10⁻⁴	MKRN3	LRT-2df	-	Yes	0	Yes	No
chr15:93652578-93653048	471	5	4.20 × 10⁻⁷	RGMA	linear	+	No	−20,135	No	n/a
chr15:101389974-101390350	377	5	3.99 × 10⁻⁴	ALDH1A3	LRT-2df	-	No	−29,659	Yes	Yes
chr16:66400320-66400599	280	8	5.17 × 10⁻⁵	CDH5	both	+	Yes	0	No	No
chr16:67233432-67233983	552	7	1.32 × 10⁻⁵	ELMO3	LRT-2df	-	No	20	No	No
chr17:6899085-6899758	674	12	1.31 × 10⁻¹³	ALOX12	both	+	Yes	0	No	No
chr17:9862752-9863081	330	10	9.06 × 10⁻³	GAS7	LRT-2df	-	Yes	0	Yes	Yes
chr17:38935747-38936092	346	5	2.50 × 10⁻⁴	KRT27	LRT-2df	+	No	2694	Yes	Yes
chr17:47571835-47572132	298	5	8.26 × 10⁻³	NGFR	both	+	Yes	−523	Yes	No
chr18:77623282-77623598	317	7	6.08 × 10⁻³	KCNG2	linear	+	Yes	−70	No	n/a
chr19:45504242-45504516	275	6	2.69 × 10⁻³	RELB	LRT-2df	-	Yes	−191	Yes	No
chr19:49198900-49199234	335	5	1.71 × 10⁻⁴	FUT2	LRT-2df	+	Yes	0	No	No
chr21:37915044-37915391	348	10	8.64 × 10⁻⁴	CLDN14	both	+	Yes	0	No	No
chr22:44568725-44568913	189	6	7.20 × 10⁻³	PARVG	LRT-2df	+	Yes	0	Yes	No

Genome build: GRCh37/hg19. The DMRs were identified by the comb-p method based on the results of linear regression or LRT-2df. A region was identified as a DMR if it had a Šidák p-value < 0.01 and at least 5 CpG sites.
bp base pair, DMR differentially methylated regions, n/a not applied, TSS transcription starting site, LRT-2df likelihood ratio test with 2 degree of freedom.
^aStatistical model in which the DMR was discovered: “linear” represents linear regression without accounting for interaction between asthma and rhinovirus infection; “LRT-2df” represents 2 degree of freedom likelihood ratio test accounting for interaction between asthma and rhinovirus infection; “both” represents that the DMR was identified by both models (in such case, results with more CpG sites were presented).
^bDistance to transcription starting site: a negative number means the DMR is upstream from the TSS; a positive number means the DMR is downstream from the TSS.
^cDirection of effect was obtained from linear regression or LRT-2df for the main effect of asthma. A + represents higher methylation in asthma cases compared to non-cases among infants without rhinovirus infection; a – represents lower methylation level in asthma cases compared to non-cases among infants without rhinovirus infection. In the case when the direction of effect was inconsistent across CpG sites within a DMR, we took the direction of the average of coefficients across the CpG sites.
^dEvidence for open chromatin was obtained by single cell ATAC-seq peak in human peripheral blood mononuclear cells (PBMCs) from a healthy donor.
^eFor DMRs identified by LRT-2df, we obtained the nominal p-value for the interaction term asthma*rhinovirus infection. A “Yes” represents that interaction-p < 0.05 for more than half of the CpG sites in that DMR. Gene names are italicized.

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Table 2 Differentially methylated regions (DMRs, Šidák p-value < 0.01) associated with asthma at 6 years among infants hospitalized for bronchiolitis (n = 506)

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