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

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    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.
    Show allShow less
    Issue Date
    2014-10-31
    Subjects
    CHRND
    CPOX
    DNA methylation
    epigenome-wide screen
    gene network
    metQTLs
    smoking
    
    Metadata
    Show full item record
    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.
    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 & Francis
    Journal
    Epigenetics
    URI
    http://hdl.handle.net/10547/623114
    DOI
    10.4161/15592294.2014.969637
    PubMed ID
    25424692
    PubMed Central ID
    PMC4623553
    Additional Links
    https://www.tandfonline.com/doi/full/10.4161/15592294.2014.969637
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623553/
    Type
    Article
    Language
    en
    ISSN
    1559-2308
    ae974a485f413a2113503eed53cd6c53
    10.4161/15592294.2014.969637
    Scopus Count
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