05010nas a2201129 4500008004100000022001400041245004800055210004700103260001300150300001200163490000600175520193900181100001902120700001902139700002502158700002102183700002502204700002402229700001702253700001202270700001902282700002302301700002902324700002302353700002302376700002102399700001802420700002102438700001702459700001902476700002002495700001702515700001302532700002102545700002002566700001402586700002302600700001802623700002002641700001902661700001602680700002602696700001402722700002102736700002002757700002202777700002302799700001902822700001902841700002002860700002502880700002502905700002502930700001502955700002002970700001802990700002403008700002803032700001903060700001903079700002003098700001603118700002303134700002303157700002503180700002503205700002303230700001803253700002103271700002103292700002503313700002003338700002003358700002003378700002403398700001803422700001903440700002403459700001903483700002203502700002303524700002203547700002403569700001803593700002603611700002603637700002103663700002103684700001603705700001703721700002603738700001803764700002003782700001703802700002503819856003603844 2016 eng d a1942-326800aEpigenetic Signatures of Cigarette Smoking.0 aEpigenetic Signatures of Cigarette Smoking c2016 Oct a436-4470 v93 a
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<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.
1 aJoehanes, Roby1 aJust, Allan, C1 aMarioni, Riccardo, E1 aPilling, Luke, C1 aReynolds, Lindsay, M1 aMandaviya, Pooja, R1 aGuan, Weihua1 aXu, Tao1 aElks, Cathy, E1 aAslibekyan, Stella1 aMoreno-Macias, Hortensia1 aSmith, Jennifer, A1 aBrody, Jennifer, A1 aDhingra, Radhika1 aYousefi, Paul1 aPankow, James, S1 aKunze, Sonja1 aShah, Sonia, H1 aMcRae, Allan, F1 aLohman, Kurt1 aSha, Jin1 aAbsher, Devin, M1 aFerrucci, Luigi1 aZhao, Wei1 aDemerath, Ellen, W1 aBressler, Jan1 aGrove, Megan, L1 aHuan, Tianxiao1 aLiu, Chunyu1 aMendelson, Michael, M1 aYao, Chen1 aKiel, Douglas, P1 aPeters, Annette1 aWang-Sattler, Rui1 aVisscher, Peter, M1 aWray, Naomi, R1 aStarr, John, M1 aDing, Jingzhong1 aRodriguez, Carlos, J1 aWareham, Nicholas, J1 aIrvin, Marguerite, R1 aZhi, Degui1 aBarrdahl, Myrto1 aVineis, Paolo1 aAmbatipudi, Srikant1 aUitterlinden, André, G1 aHofman, Albert1 aSchwartz, Joel1 aColicino, Elena1 aHou, Lifang1 aVokonas, Pantel, S1 aHernandez, Dena, G1 aSingleton, Andrew, B1 aBandinelli, Stefania1 aTurner, Stephen, T1 aWare, Erin, B1 aSmith, Alicia, K1 aKlengel, Torsten1 aBinder, Elisabeth, B1 aPsaty, Bruce, M1 aTaylor, Kent, D1 aGharib, Sina, A1 aSwenson, Brenton, R1 aLiang, Liming1 aDeMeo, Dawn, L1 aO'Connor, George, T1 aHerceg, Zdenko1 aRessler, Kerry, J1 aConneely, Karen, N1 aSotoodehnia, Nona1 aKardia, Sharon, L R1 aMelzer, David1 aBaccarelli, Andrea, A1 avan Meurs, Joyce, B J1 aRomieu, Isabelle1 aArnett, Donna, K1 aOng, Ken, K1 aLiu, Yongmei1 aWaldenberger, Melanie1 aDeary, Ian, J1 aFornage, Myriam1 aLevy, Daniel1 aLondon, Stephanie, J uhttps://chs-nhlbi.org/node/7261