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Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population
Authors:Xiaoyan Zhu  Jun Li  Siyun Deng  Kuai Yu  Xuezhen Liu  Qifei Deng  Huizhen Sun  Xiaomin Zhang  Meian He  Huan Guo  Weihong Chen  Jing Yuan  Bing Zhang  Dan Kuang  Xiaosheng He  Yansen Bai  Xu Han  Bing Liu  Xiaoliang Li  Liangle Yang  Haijing Jiang  Yizhi Zhang  Jie Hu  Longxian Cheng  Xiaoting Luo  Wenhua Mei  Zhiming Zhou  Shunchang Sun  Liyun Zhang  Chuanyao Liu  Yanjun Guo  Zhihong Zhang  Frank B. Hu  Liming Liang  Tangchun Wu
Abstract:

Background:

Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited.

Objectives:

We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population.

Methods:

We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes.

Results:

We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking.

Conclusion:

We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation.

Citation:

Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.1509834
Keywords:
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