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dc.contributor.authorTsaprouni, Loukia G.en
dc.contributor.authorYang, Tsun-Poen
dc.contributor.authorBell, Jordanaen
dc.contributor.authorDick, Katherine J.en
dc.contributor.authorKanoni, Stavroulaen
dc.contributor.authorNisbet, Jamesen
dc.contributor.authorViñuela, Anaen
dc.contributor.authorGrundberg, Elinen
dc.contributor.authorNelson, Christopher P.en
dc.contributor.authorMeduri, Eshwaren
dc.contributor.authorBuil, Alfonsoen
dc.contributor.authorCambien, Francoisen
dc.contributor.authorHengstenberg, Christianen
dc.contributor.authorErdmann, Jeanetteen
dc.contributor.authorSchunkert, Heriberten
dc.contributor.authorOuwehand, Willem H.en
dc.contributor.authorGoodall, Alison H.en
dc.contributor.authorSpector, Tim D.en
dc.contributor.authorDermitzakis, Emmanouilen
dc.contributor.authorDeloukas, Panosen
dc.contributor.authorSamani, Nilesh J.en
dc.date.accessioned2019-01-29T10:57:54Z
dc.date.available2019-01-29T10:57:54Z
dc.date.issued2014-10-31
dc.identifier.citationTsaprouni LG, Yang T-P, Bell J, Dick KJ, Kanoni S, Nisbet J, Viñuela A, Grundberg E, Nelson CP, Meduri E, Buil A, Cambien F, Hengstenberg C, Erdmann J, Schunkert H, Ouwehand WH, Goodall AH, Spector TD, Dermitzakis E, Deloukas P, Samani NJ (2014) 'Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.', Epigenetics, 9 (10), pp.1382-96.en
dc.identifier.issn1559-2308
dc.identifier.pmid25424692
dc.identifier.doi10.4161/15592294.2014.969637
dc.identifier.urihttp://hdl.handle.net/10547/623114
dc.description.abstractSmoking is a major risk factor in many diseases. Genome wide association studies have linked genes for nicotine dependence and smoking behavior to increased risk of cardiovascular, pulmonary, and malignant diseases. We conducted an epigenome wide association study in peripheral-blood DNA in 464 individuals (22 current smokers and 263 ex-smokers), using the Human Methylation 450 K array. Upon replication in an independent sample of 356 twins (41 current and 104 ex-smokers), we identified 30 probes in 15 distinct loci, all of which reached genome-wide significance in the combined analysis P < 5 × 10(-8). All but one probe (cg17024919) remained significant after adjusting for blood cell counts. We replicated all 9 known loci and found an independent signal at CPOX near GPR15. In addition, we found 6 new loci at PRSS23, AVPR1B, PSEN2, LINC00299, RPS6KA2, and KIAA0087. Most of the lead probes (13 out of 15) associated with cigarette smoking, overlapped regions of open chromatin (FAIRE and DNaseI hypersensitive sites) or/and H3K27Ac peaks (ENCODE data set), which mark regulatory elements. The effect of smoking on DNA methylation was partially reversible upon smoking cessation for longer than 3 months. We report the first statistically significant interaction between a SNP (rs2697768) and cigarette smoking on DNA methylation (cg03329539). We provide evidence that the metSNP for cg03329539 regulates expression of the CHRND gene located circa 95 Kb downstream of the methylation site. Our findings suggest the existence of dynamic, reversible site-specific methylation changes in response to cigarette smoking , which may contribute to the extended health risks associated with cigarette smoking.
dc.language.isoenen
dc.publisherTaylor & Francisen
dc.relation.urlhttps://www.tandfonline.com/doi/full/10.4161/15592294.2014.969637en
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623553/en
dc.subjectCHRNDen
dc.subjectCPOXen
dc.subjectDNA methylationen
dc.subjectepigenome-wide screenen
dc.subjectgene networken
dc.subjectmetQTLsen
dc.subjectsmokingen
dc.titleCigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessationen
dc.typeArticleen
dc.identifier.journalEpigeneticsen
dc.identifier.pmcidPMC4623553
dc.date.updated2019-01-29T10:51:53Z
html.description.abstractSmoking is a major risk factor in many diseases. Genome wide association studies have linked genes for nicotine dependence and smoking behavior to increased risk of cardiovascular, pulmonary, and malignant diseases. We conducted an epigenome wide association study in peripheral-blood DNA in 464 individuals (22 current smokers and 263 ex-smokers), using the Human Methylation 450 K array. Upon replication in an independent sample of 356 twins (41 current and 104 ex-smokers), we identified 30 probes in 15 distinct loci, all of which reached genome-wide significance in the combined analysis P < 5 × 10(-8). All but one probe (cg17024919) remained significant after adjusting for blood cell counts. We replicated all 9 known loci and found an independent signal at CPOX near GPR15. In addition, we found 6 new loci at PRSS23, AVPR1B, PSEN2, LINC00299, RPS6KA2, and KIAA0087. Most of the lead probes (13 out of 15) associated with cigarette smoking, overlapped regions of open chromatin (FAIRE and DNaseI hypersensitive sites) or/and H3K27Ac peaks (ENCODE data set), which mark regulatory elements. The effect of smoking on DNA methylation was partially reversible upon smoking cessation for longer than 3 months. We report the first statistically significant interaction between a SNP (rs2697768) and cigarette smoking on DNA methylation (cg03329539). We provide evidence that the metSNP for cg03329539 regulates expression of the CHRND gene located circa 95 Kb downstream of the methylation site. Our findings suggest the existence of dynamic, reversible site-specific methylation changes in response to cigarette smoking , which may contribute to the extended health risks associated with cigarette smoking.


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