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ABSTRACT: Background
Smoking increases the risk of many diseases, and it is also linked to blood DNA methylation changes that may be important in disease etiology.Objectives
We sought to identify novel CpG sites associated with cigarette smoking.Methods
We used two epigenome-wide data sets from the Sister Study to identify and confirm CpG sites associated with smoking. One included 908 women with methylation measurements at 27,578 CpG sites using the HumanMethylation27 BeadChip; the other included 200 women with methylation measurements for 473,844 CpG sites using the HumanMethylation450 BeadChip. Significant CpGs from the second data set that were not included in the 27K assay were validated by pyrosequencing in a subset of 476 samples from the first data set.Results
Our study successfully confirmed smoking associations for 9 previously established CpGs and identified 2 potentially novel CpGs: cg26764244 in GNG12 (p = 9.0 × 10-10) and cg22335340 in PTPN6 (p = 2.9 × 10-05). We also found strong evidence of an association between smoking status and cg02657160 in CPOX (p = 7.3 × 10-7), which has not been previously reported. All 12 CpGs were undermethylated in current smokers and showed an increasing percentage of methylation in former and never-smokers.Conclusions
We identified 2 potentially novel smoking related CpG sites, and provided independent replication of 10 previously reported CpGs sites related to smoking, one of which is situated in the gene CPOX. The corresponding enzyme is involved in heme biosynthesis, and smoking is known to increase heme production. Our study extends the evidence base for smoking-related changes in DNA methylation.
SUBMITTER: Harlid S
PROVIDER: S-EPMC4080519 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Harlid Sophia S Xu Zongli Z Panduri Vijayalakshmi V Sandler Dale P DP Taylor Jack A JA
Environmental health perspectives 20140404 7
<h4>Background</h4>Smoking increases the risk of many diseases, and it is also linked to blood DNA methylation changes that may be important in disease etiology.<h4>Objectives</h4>We sought to identify novel CpG sites associated with cigarette smoking.<h4>Methods</h4>We used two epigenome-wide data sets from the Sister Study to identify and confirm CpG sites associated with smoking. One included 908 women with methylation measurements at 27,578 CpG sites using the HumanMethylation27 BeadChip; th ...[more]