DNA methylation and smoking in Korean adults: epigenome-wide association study.
Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases. However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood. Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes. There are few data on regional methylation changes in relation to smoking. Few data link differential methylation in blood to differential gene expression in lung tissue.



We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing correctedp< 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n= 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip. Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking. Of the 87 DMRs, 66 were mapped to novel loci. Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs. Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank,n= 188).



Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking. Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.
Epidemiology Branch, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, Durham, NC 27709 USA.|Institute of Medical Science, Kangwon National University, Chuncheon-si, Gangwon-do 24341 South Korea.|Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon-si, Gangwon-do 19300 South Korea.
Mi Kyeong
MK
Lee
Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon-si, Gangwon-do 19300 South Korea.
Yoonki
Y
Hong
Institute of Health and Environment, Seoul National University, Seoul, 08826 South Korea.
Sun-Young
SY
Kim
Epidemiology Branch, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, Durham, NC 27709 USA.
Stephanie J
SJ
London
Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon-si, Gangwon-do 19300 South Korea.
Woo Jin
WJ
Kim
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D003367:Cotinine / Q000652:urine; D019175:DNA Methylation; D057890:Epigenomics / Q000379:methods*; D005260:Female; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000235:genetics* / Q000652:urine; D016540:Smoking Cessation
D003367:Cotinine
Cotinine; DNA methylation; Duration of smoking cessation; Epigenome-wide association study; Gene expression; Smoking
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