DNA methylation and smoking in Korean adults: epigenome-wide association study.
DNA methylation and smoking in Korean adults: epigenome-wide association study.
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DOI：
10.1186/s13148-016-0266-6
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发表时间：
2016
影响因子：
5.7
通讯作者：
Kim WJ
中科院分区：
文献类型：
--
作者：
Lee MK;Hong Y;Kim SY;London SJ;Kim WJ
吸烟会增加患癌症、心血管和肺部疾病的风险。然而，吸烟如何增加疾病风险的潜在机制尚不完全清楚。全表观基因组关联研究（EWASs）主要在非亚洲人群中进行，目的是在单个探针上确定与吸烟相关的甲基化改变。很少有数据表明区域甲基化变化与吸烟有关。很少有数据将血液中的差异甲基化与肺组织中的差异基因表达联系起来。我们使用Illumina HumanMethylation450 BeadChip对来自韩国慢性阻塞性肺病队列（n = 100，包括31名当前吸烟者、30名既往吸烟者和39名从未吸烟者）的可替宁验证的血液DNA进行EWAS，与从不吸烟者相比，我们鉴定出108个显著（错误发现率(FDR) < 0.05）差异甲基化探针（dmp）和87个显著差异甲基化区域（DMRs）（多重检验校正p < 0.01）。在108个dmp （FDR < 0.05）中，根据Bonferroni校正，9个CpGs具有统计学意义，93个CpGs是新发现的，其中5个定位于以前与吸烟相关的位点。在87个DMRs中，66个被定位到新的位点。甲基化与当前吸烟者6个dmp时尿可替宁水平相关，与当前吸烟者6个dmp时的包年相关，与前吸烟者8个dmp时的戒烟持续时间相关。在我们的显著dmp或DMRs注释的143个基因中，20个基因的基因表达水平与吸烟者肺组织转录组数据中的包年相关（Asan Biobank, n = 188）。我们对韩国人差异甲基化的研究证实了之前在非亚洲人群中的发现，并揭示了与吸烟有关的新位点。血液中与吸烟相关的甲基化差异与肺组织中的基因表达相关，而肺组织是吸烟对健康不良影响的重要靶点，这支持了甲基化在吸烟相关疾病中的潜在功能重要性。本文的在线版本（doi:10.1186/s13148-016-0266-6）包含补充材料，可供授权用户使用。
Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases. However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood. Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes. There are few data on regional methylation changes in relation to smoking. Few data link differential methylation in blood to differential gene expression in lung tissue. We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip. Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking. Of the 87 DMRs, 66 were mapped to novel loci. Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs. Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188). Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking. Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease. The online version of this article (doi:10.1186/s13148-016-0266-6) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Marabita F;Almgren M;Lindholm ME;Ruhrmann S;Fagerström-Billai F;Jagodic M;Sundberg CJ;Ekström TJ;Teschendorff AE;Tegnér J;Gomez-Cabrero D
通讯作者：
Gomez-Cabrero D
影响因子：
3.7
作者：
Allione A;Marcon F;Fiorito G;Guarrera S;Siniscalchi E;Zijno A;Crebelli R;Matullo G
通讯作者：
Matullo G
影响因子：
3.5
作者：
Besingi, Welisane;Johansson, Asa
通讯作者：
Johansson, Asa
影响因子：
168.9
作者：
Dick, Katherine J.;Nelson, Christopher P.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily