Epigenetic Signatures of Cigarette Smoking.
Epigenetic Signatures of Cigarette Smoking.
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吸烟的表观遗传签名。
DOI：
10.1161/circgenetics.116.001506
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
London SJ
中科院分区：
文献类型：
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作者：
Joehanes R;Just AC;Marioni RE;Pilling LC;Reynolds LM;Mandaviya PR;Guan W;Xu T;Elks CE;Aslibekyan S;Moreno-Macias H;Smith JA;Brody JA;Dhingra R;Yousefi P;Pankow JS;Kunze S;Shah SH;McRae AF;Lohman K;Sha J;Absher DM;Ferrucci L;Zhao W;Demerath EW;Bressler J;Grove ML;Huan T;Liu C;Mendelson MM;Yao C;Kiel DP;Peters A;Wang-Sattler R;Visscher PM;Wray NR;Starr JM;Ding J;Rodriguez CJ;Wareham NJ;Irvin MR;Zhi D;Barrdahl M;Vineis P;Ambatipudi S;Uitterlinden AG;Hofman A;Schwartz J;Colicino E;Hou L;Vokonas PS;Hernandez DG;Singleton AB;Bandinelli S;Turner ST;Ware EB;Smith AK;Klengel T;Binder EB;Psaty BM;Taylor KD;Gharib SA;Swenson BR;Liang L;DeMeo DL;O'Connor GT;Herceg Z;Ressler KJ;Conneely KN;Sotoodehnia N;Kardia SL;Melzer D;Baccarelli AA;van Meurs JB;Romieu I;Arnett DK;Ong KK;Liu Y;Waldenberger M;Deary IJ;Fornage M;Levy D;London SJ
DNA甲基化留下了吸烟暴露的长期特征，是烟草暴露易导致不良健康结果（如癌症、骨质疏松症、肺病和心血管疾病）的一种潜在机制。为了全面确定吸烟与DNA甲基化之间的关系，我们使用Illumina BeadChip 450K阵列对来自16个队列参与者的15,907份血液DNA样本进行了全基因组DNA甲基化评估的荟萃分析（包括2,433名吸烟者，6,518名戒烟者和6,956名从不吸烟者）。在Bonferroni阈值p<1×10−7（错误发现率(FDR)<0.05时，18,760个CpGs甲基化）下，目前吸烟者与从不吸烟者相比，2,623个CpG位点（CpGs），注释到1,405个基因，具有统计学显著差异。在全基因组研究中，这些CpGs上注释的基因与肺功能、癌症、炎症性疾病和心脏病等几种与吸烟相关的特征相关。将吸烟者与从不吸烟者进行比较，目前吸烟者与从不吸烟者之间的185个CpGs差异显著p<1×10 - 7 (FDR时2,623个CpGs <0.05)，表明戒烟后甲基化持续改变，且减弱。转录组整合鉴定了许多差异甲基化CpGs对基因表达的影响。吸烟对全基因组甲基化有广泛的影响，在许多位点上，这种影响在戒烟后仍持续多年。许多差异甲基化基因是吸烟生物学效应方面的新基因，可能代表预防或治疗烟草相关疾病的治疗靶点。这些位点的甲基化也可以作为终生暴露于烟草烟雾的敏感和稳定的生物标志物。
DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers). Comparing current versus never smokers, 2,623 CpG sites (CpGs), annotated to 1,405 genes, were statistically significantly differentially methylated at Bonferroni threshold of p<1×10−7 (18,760 CpGs at False Discovery Rate (FDR)<0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant p<1×10−7 (2,623 CpGs at FDR<0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biologic effects of smoking, and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.