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Epigenetic Signatures of Cigarette Smoking.

TitleEpigenetic Signatures of Cigarette Smoking.
Publication TypeJournal Article
Year of Publication2016
AuthorsJoehanes R, Just AC, Marioni RE, Pilling LC, Reynolds LM, Mandaviya PR, Guan W, Xu T, Elks CE, Aslibekyan S, Moreno-Macias H, Smith JA, Brody JA, Dhingra R, Yousefi P, Pankow JS, Kunze S, Shah SH, McRae AF, Lohman K, Sha J, Absher DM, Ferrucci L, Zhao W, Demerath EW, Bressler J, Grove ML, Huan T, Liu C, Mendelson MM, Yao C, Kiel DP, Peters A, Wang-Sattler R, Visscher PM, Wray NR, Starr JM, Ding J, Rodriguez CJ, Wareham NJ, Irvin MR, Zhi D, Barrdahl M, Vineis P, Ambatipudi S, Uitterlinden AG, Hofman A, Schwartz J, Colicino E, Hou L, Vokonas PS, Hernandez DG, Singleton AB, Bandinelli S, Turner ST, Ware EB, Smith AK, Klengel T, Binder EB, Psaty BM, Taylor KD, Gharib SA, Swenson BR, Liang L, DeMeo DL, O'Connor GT, Herceg Z, Ressler KJ, Conneely KN, Sotoodehnia N, Kardia SLR, Melzer D, Baccarelli AA, van Meurs JBJ, Romieu I, Arnett DK, Ong KK, Liu Y, Waldenberger M, Deary IJ, Fornage M, Levy D
Secondary AuthorsLondon SJ
JournalCirc Cardiovasc Genet
Volume9
Issue5
Pagination436-447
Date Published2016 Oct
ISSN1942-3268
KeywordsAged, Case-Control Studies, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Profiling, Genetic Markers, Genome-Wide Association Study, Genotype, Humans, Leukocytes, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Phenotype, Smoking, Smoking Cessation, Smoking Prevention, Time Factors, Transcriptome
Abstract

BACKGROUND: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.

METHODS AND RESULTS: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P

CONCLUSIONS: Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

DOI10.1161/CIRCGENETICS.116.001506
Alternate JournalCirc Cardiovasc Genet
PubMed ID27651444
PubMed Central IDPMC5267325
Grant ListETM/55 / / Chief Scientist Office / United Kingdom
CZB/4/505 / / Chief Scientist Office / United Kingdom
P50 HL120163 / HL / NHLBI NIH HHS / United States
R01 HL104135 / HL / NHLBI NIH HHS / United States
Z01 ES043012-09 / / Intramural NIH HHS / United States
R01 HL101250 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
R01 AR041398 / AR / NIAMS NIH HHS / United States
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
U01 HL072524 / HL / NHLBI NIH HHS / United States
P30 ES023515 / ES / NIEHS NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
R00 ES023450 / ES / NIEHS NIH HHS / United States