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  Epigenetic Signatures of Cigarette Smoking

Joehanes, R., Just, A. C., Marioni, R. E., Pilling, L. C., Reynolds, L. M., Mandaviya, P. R., et al. (2016). Epigenetic Signatures of Cigarette Smoking. CIRCULATION-CARDIOVASCULAR GENETICS, 9(5), 436-447. doi:10.1161/CIRCGENETICS.116.001506.

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Joehanes, Roby1, Author
Just, Allan C.1, Author
Marioni, Riccardo E.1, Author
Pilling, Luke C.1, Author
Reynolds, Lindsay M.1, Author
Mandaviya, Pooja R.1, Author
Guan, Weihua1, Author
Xu, Tao1, Author
Elks, Cathy E.1, Author
Aslibekyan, Stella1, Author
Moreno-Macias, Hortensia1, Author
Smith, Jennifer A.1, Author
Brody, Jennifer A.1, Author
Dhingra, Radhika1, Author
Yousefi, Paul1, Author
Pankow, James S.1, Author
Kunze, Sonja1, Author
Shah, Sonia H.1, Author
McRae, Allan F.1, Author
Lohman, Kurt1, Author
Sha, Jin1, AuthorAbsher, Devin M.1, AuthorFerrucci, Luigi1, AuthorZhao, Wei1, AuthorDemerath, Ellen W.1, AuthorBressler, Jan1, AuthorGrove, Megan L.1, AuthorHuan, Tianxiao1, AuthorLiu, Chunyu1, AuthorMendelson, Michael M.1, AuthorYao, Chen1, AuthorKiel, Douglas P.1, AuthorPeters, Annette1, AuthorWang-Sattler, Rui1, AuthorVisscher, Peter M.1, AuthorWray, Naomi R.1, AuthorStarr, John M.1, AuthorDing, Jingzhong1, AuthorRodriguez, Carlos J.1, AuthorWareham, Nicholas J.1, AuthorIrvin, Marguerite R.1, AuthorZhi, Degui1, AuthorBarrdahl, Myrto1, AuthorVineis, Paolo1, AuthorAmbatipudi, Srikant1, AuthorUitterlinden, Andre G.1, AuthorHofman, Albert1, AuthorSchwartz, Joel1, AuthorColicino, Elena1, AuthorHou, Lifang1, AuthorVokonas, Pantel S.1, AuthorHernandez, Dena G.1, AuthorSingleton, Andrew B.1, AuthorBandinelli, Stefania1, AuthorTurner, Stephen T.1, AuthorWare, Erin B.1, AuthorSmith, Alicia K.1, AuthorKlengel, Torsten2, Author              Binder, Elisabeth B.2, Author              Psaty, Bruce M.1, AuthorTaylor, Kent D.1, AuthorGharib, Sina A.1, AuthorSwenson, Brenton R.1, AuthorLiang, Liming1, AuthorDeMeo, Dawn L.1, AuthorO'Connor, George T.1, AuthorHerceg, Zdenko1, AuthorRessler, Kerry J.1, AuthorConneely, Karen N.1, AuthorSotoodehnia, Nona1, AuthorKardia, Sharon L. R.1, AuthorMelzer, David1, AuthorBaccarelli, Andrea A.1, Authorvan Meurs, Joyce B. J.1, AuthorRomieu, Isabelle1, AuthorArnett, Donna K.1, AuthorOng, Ken K.1, AuthorLiu, Yongmei1, AuthorWaldenberger, Melanie1, AuthorDeary, Ian J.1, AuthorFornage, Myriam1, AuthorLevy, Daniel1, AuthorLondon, Stephanie J.1, Author more..
1external, ou_persistent22              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              


Free keywords: biomarkers, genome-wide association study, meta-analysis, methylation, smoking
 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 15907 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<1x10(-7) (18760 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<1x10(-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.


Language(s): eng - English
 Dates: 2016-10
 Publication Status: Published in print
 Pages: -
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Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 9 (5) Sequence Number: - Start / End Page: 436 - 447 Identifier: ISSN: 1942-325X