Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation
Authors
Tsaprouni, Loukia G.Yang, Tsun-Po
Bell, Jordana
Dick, Katherine J.
Kanoni, Stavroula
Nisbet, James
Viñuela, Ana
Grundberg, Elin
Nelson, Christopher P.
Meduri, Eshwar
Buil, Alfonso
Cambien, Francois
Hengstenberg, Christian
Erdmann, Jeanette
Schunkert, Heribert
Ouwehand, Willem H.
Goodall, Alison H.
Spector, Tim D.
Dermitzakis, Emmanouil
Deloukas, Panos
Samani, Nilesh J.
Issue Date
2014-10-31
Metadata
Show full item recordAbstract
Smoking 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.Citation
Tsaprouni 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.Publisher
Taylor & FrancisJournal
EpigeneticsPubMed ID
25424692PubMed Central ID
PMC4623553Additional Links
https://www.tandfonline.com/doi/full/10.4161/15592294.2014.969637https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623553/
Type
ArticleLanguage
enISSN
1559-2308ae974a485f413a2113503eed53cd6c53
10.4161/15592294.2014.969637
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