Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation

Tsaprouni, Loukia and Yang, Tsun-Po and Bell, Jordana and Dick, Katherine J and Kanoni, Stavroula and Nisbet, James and Viñuela, Ana and Grundberg, Elin and Nelson, Christopher P and Meduri, Eshwar and Buil, Alfonso and Cambien, Francois and Hengstenberg, Christian and Erdmann, Jeanette and Schunkert, Heribert and Goodall, Alison H and Ouwehand, Willem H and Dermitzakis, Emmanouil and Spector, Tim D and Samani, Nilesh J and Deloukas, Panos (2014) Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics, 9 (10). pp. 1382-1396. ISSN 1559-2308

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Abstract

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.

Item Type: Article
Subjects: A100 Pre-clinical Medicine
C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
C900 Others in Biological Sciences
Divisions: Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Loukia Tsaprouni
Date Deposited: 04 Jul 2017 09:22
Last Modified: 04 Jul 2017 09:22
URI: http://www.open-access.bcu.ac.uk/id/eprint/4782

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