Table 2.

Candidate SM-DMRs identified by RRBS analysis in CRU and MESA groups selected for validation in the CRU-Pyro group.

SM-DMR Nearest Gene Transcription Start	Chr	DMR start	Number of CpGs in DMR	450K covered CpGs	450K smoking CpGs	$\mathrm{\Delta }\text{Meth}$a (%)	RRBS b Combined p-value	Group Signif c	Valid	H3 K27ac	DNaseI TFBS	Biological function/diseasesd	References
ALPPL2	Chr2	233283913	65	3	3	$-10$	$8.99\times {10}^{-20}$	CRU M C	$+$	$+$	$+$	Aging, breast cancer	Salpea et al. 2012; Dua et al. 2013
AHRR	Chr5	373377	5	1	1	$-42$	$3.06\times {10}^{-19}$	CRU M C	$+$	$+$	$+$	Atherosclerosis, immunity	Reynolds et al. 2015; Zhang et al. 2017
LRP5	Chr11	68148288	3	0	0	$-9$	$2.19\times {10}^{-07}$	CRU M C	$+$	$+$	$+$	Atherosclerosis	Borrell-Pages et al. 2014
PPP1R15A	Chr19	49379722	9	0	0	$-13$	$4.12\times {10}^{-07}$	CRU M C	$+$	$+$	$+$	Peripheral arterial disease	Masud et al. 2012
SLC24A3	Chr20	19193923	9	1	1	$-7$	$9.39\times {10}^{-06}$	M C	$+$	—	$+$	Obesity, hypertension,	Logsdon et al. 2012; Mick et al. 2011
SASH1	Chr6	148684696	4	0	0	$-5$	$1.50\times {10}^{-04}$	M C	F	$+$	$+$	Atherosclerosis	Weidmann et al. 2015
RDX	Chr11	110079735	25	0	0	20	$1.90\times {10}^{-04}$	C	NS	—	$+$	Deafness	Kitajiri et al. 2004
C5orf55-EXOC-AS	Chr5	403252	3	0	0	$-11$	$2.09\times {10}^{-04}$	CRU C	$+$	$+$	$+$	—	—
F2RL3-CPAMD8	Chr19	17004139	15	0	0	$-6$	$1.50\times {10}^{-04}$	CRU C	$+$	—	$+$	Cardiovascular disease, cancer	Fasanelli et al. 2015; Muka et al. 2016; Zhang et al. 2016
F2RL3	Chr19	17000053	9	0	0	$-3$	$1.90\times {10}^{-04}$	CRU M C	$+$	$+$	$+$	Cardiovascular disease, cancer	Zhang et al. 2016; Fasanelli et al. 2015; Muka et al. 2016
HOXA5	Chr7	27184187	42	16	0	$-7$	$1.51\times {10}^{-02}$	—	NS	$+$	$+$	Atherosclerosis	Dunn et al. 2014
Total			189	21	5

Note: —, not applicable; 450K covered, CpGs within DMR on the Illumina Human 450K Methylation Array; 450K smoking CpGs, CpGs within the DMR on the Illumina Human 450K Methylation Array associated with smoking; C, combined CRU-MESA; C, CRU; Chr, Chromosome; CRU, Clinical Research Unit; DMR start, Transcription start site; DMR, differentially methylated region; DNaseI, DNase I hypersensitivity region; F, assay design failure; H3K27ac, Histone 3, Lysine 27 acetylation; M, MESA; MESA, Multi-Ethnic Study of Atherosclerosis; NS, not significant; RRBS, reduced representation bisulfite sequencing; SM, smoking associated; TFBS, transcription factor binding site.

^a$\mathrm{\Delta }$ Meth Diff, average methylation difference between smoking and nonsmoker.

^bSM-DMR p-value for the Combined CRU-MESA RRBS analysis.

^cAnalysis groups where DMR was observed as significant: CRU, M, C analysis.

^dReported disease association or possible biological function as reported in listed reference.