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dc.contributor.authorJoehanes, Ren
dc.contributor.authorJust, ACen
dc.contributor.authorMarioni, REen
dc.contributor.authorPilling, LCen
dc.contributor.authorReynolds, LMen
dc.contributor.authorMandaviya, PRen
dc.contributor.authorGuan, Wen
dc.contributor.authorXu, Ten
dc.contributor.authorElks, Cathyen
dc.contributor.authorAslibekyan, Sen
dc.contributor.authorMoreno-Macias, Hen
dc.contributor.authorSmith, JAen
dc.contributor.authorBrody, JAen
dc.contributor.authorDhingra, Ren
dc.contributor.authorYousefi, Pen
dc.contributor.authorPankow, JSen
dc.contributor.authorKunze, Sen
dc.contributor.authorShah, SHen
dc.contributor.authorMcRae, AFen
dc.contributor.authorLohman, Ken
dc.contributor.authorSha, Jen
dc.contributor.authorAbsher, DMen
dc.contributor.authorFerrucci, Len
dc.contributor.authorZhao, Wen
dc.contributor.authorDemerath, EWen
dc.contributor.authorBressler, Jen
dc.contributor.authorGrove, MLen
dc.contributor.authorHuan, Ten
dc.contributor.authorLiu, Cen
dc.contributor.authorMendelson, MMen
dc.contributor.authorYao, Cen
dc.contributor.authorKiel, DPen
dc.contributor.authorPeters, Aen
dc.contributor.authorWang-Sattler, Ren
dc.contributor.authorVisscher, PMen
dc.contributor.authorWray, NRen
dc.contributor.authorStarr, JMen
dc.contributor.authorDing, Jen
dc.contributor.authorRodriguez, CJen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorIrvin, MRen
dc.contributor.authorZhi, Den
dc.contributor.authorBarrdahl, Men
dc.contributor.authorVineis, Pen
dc.contributor.authorAmbatipudi, Sen
dc.contributor.authorUitterlinden, AGen
dc.contributor.authorHofman, Aen
dc.contributor.authorSchwartz, Jen
dc.contributor.authorColicino, Een
dc.contributor.authorHou, Len
dc.contributor.authorVokonas, PSen
dc.contributor.authorHernandez, DGen
dc.contributor.authorSingleton, ABen
dc.contributor.authorBandinelli, Sen
dc.contributor.authorTurner, STen
dc.contributor.authorWare, EBen
dc.contributor.authorSmith, AKen
dc.contributor.authorKlengel, Ten
dc.contributor.authorBinder, EBen
dc.contributor.authorPsaty, BMen
dc.contributor.authorTaylor, KDen
dc.contributor.authorGharib, SAen
dc.contributor.authorSwenson, BRen
dc.contributor.authorLiang, Len
dc.contributor.authorDeMeo, DLen
dc.contributor.authorO'Connor, GTen
dc.contributor.authorHerceg, Zen
dc.contributor.authorRessler, KJen
dc.contributor.authorConneely, KNen
dc.contributor.authorSotoodehnia, Nen
dc.contributor.authorKardia, SLRen
dc.contributor.authorMelzer, Den
dc.contributor.authorBaccarelli, AAen
dc.contributor.authorvan Meurs, JBJen
dc.contributor.authorRomieu, Ien
dc.contributor.authorArnett, DKen
dc.contributor.authorOng, Kennethen
dc.contributor.authorLiu, Yen
dc.contributor.authorWaldenberger, Men
dc.contributor.authorDeary, IJen
dc.contributor.authorFornage, Men
dc.contributor.authorLevy, Den
dc.contributor.authorLondon, SJen
dc.date.accessioned2016-11-03T10:57:38Z
dc.date.available2016-11-03T10:57:38Z
dc.date.issued2016-10en
dc.identifier.issn1942-325X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261011
dc.description.abstractBACKGROUND: 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<1×10$^{-7}$ (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10$^{-7}$ (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. 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.
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council, British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society, Wellcome Trust
dc.languageENGen
dc.language.isoenen
dc.publisherWolters Kluwer
dc.subjectbiomarkersen
dc.subjectgenome-wide association studyen
dc.subjectmeta-analysisen
dc.subjectmethylationen
dc.subjectsmokingen
dc.titleEpigenetic Signatures of Cigarette Smokingen
dc.typeArticle
prism.endingPage447
prism.issueIdentifier5en
prism.publicationDate2016en
prism.publicationNameCirculation: Cardiovascular Geneticsen
prism.startingPage436
prism.volume9en
dc.identifier.doi10.17863/CAM.6179
dcterms.dateAccepted2016-08-16en
rioxxterms.versionofrecord10.1161/CIRCGENETICS.116.001506en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-10en
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.identifier.eissn1942-3268
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MC_U106179471)
cam.issuedOnline2016-09-20en
rioxxterms.freetoread.startdate2017-03-20


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