Epigenetic signatures of starting and stopping smoking.
Epigenetic signatures of starting and stopping smoking.
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DOI：
10.1016/j.ebiom.2018.10.051
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发表时间：
2018-11
期刊：
影响因子：
11.1
通讯作者：
Marioni RE
中科院分区：
文献类型：
--
作者：
McCartney DL;Stevenson AJ;Hillary RF;Walker RM;Bermingham ML;Morris SW;Clarke TK;Campbell A;Murray AD;Whalley HC;Porteous DJ;Visscher PM;McIntosh AM;Evans KL;Deary IJ;Marioni RE
多项研究已经在DNA甲基化差异和暴露于香烟烟雾之间建立了强有力的联系。但DNA甲基化表型是在暴露后立即建立，还是只有在长时间暴露后才建立，目前还不太清楚。在这里，我们评估了当前吸烟者外周血样本中的DNA甲基化模式对暴露剂量和持续时间的响应，以及戒烟对前吸烟者DNA甲基化的影响。对苏格兰世代中4900多名个体的90个先前确定的与吸烟相关的CpG位点的DNA甲基化数据进行降维。基于这些甲基化模式，进行k均值聚类来识别与当前和从不吸烟状态相关的聚类。对当前吸烟者的暴露时间（作为吸烟者的年数）、前吸烟者戒烟后的时间（年数）和剂量（每天香烟数）进行了聚类分配评估。指定了两个组，分别对应从不吸烟者（97.5%的人被分配到组1）和当前吸烟者（81%的人被分配到组2）。重度吸烟者的暴露时间点为5至9 年，轻度吸烟者的暴露时间点为15至19 年。在戒烟后的第一年，低剂量前吸烟者更有可能被分配到从不吸烟者密集组。相比之下，在大多数前高剂量吸烟者被分配到从不吸烟者密集组之前，至少需要两年的时间。我们的研究结果表明，与吸烟相关的DNA甲基化变化是长期暴露于香烟烟雾的结果，并且可以在戒烟后逆转。这些特征建立和恢复的时间长短与剂量有关。如果基于DNA甲基化的吸烟状态特征可以预测吸烟相关的健康结果，我们的研究结果可能为风险分层提供额外的标准。
Multiple studies have made robust associations between differential DNA methylation and exposure to cigarette smoke. But whether a DNA methylation phenotype is established immediately upon exposure, or only after prolonged exposure is less well–established. Here, we assess DNA methylation patterns from peripheral blood samples in current smokers in response to dose and duration of exposure, along with the effects of smoking cessation on DNA methylation in former smokers. Dimensionality reduction was applied to DNA methylation data at 90 previously identified smoking–associated CpG sites for over 4900 individuals in the Generation Scotland cohort. K–means clustering was performed to identify clusters associated with current and never smoker status based on these methylation patterns. Cluster assignments were assessed with respect to duration of exposure in current smokers (years as a smoker), time since smoking cessation in former smokers (years), and dose (cigarettes per day). Two clusters were specified, corresponding to never smokers (97·5% of whom were assigned to Cluster 1) and current smokers (81·1% of whom were assigned to Cluster 2). The exposure time point from which >50% of current smokers were assigned to the smoker–enriched cluster varied between 5 and 9 years in heavier smokers and between 15 and 19 years in lighter smokers. Low–dose former smokers were more likely to be assigned to the never smoker–enriched cluster in the first year following cessation. In contrast, a period of at least two years was required before the majority of former high–dose smokers were assigned to the never smoker–enriched cluster. Our findings suggest that smoking–associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation. The length of time in which these signatures are established and recovered is dose dependent. Should DNA methylation–based signatures of smoking status be predictive of smoking–related health outcomes, our findings may provide an additional criterion on which to stratify risk.
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影响因子：
9.8
作者：
Joubert, Bonnie R.;Felix, Janine F.;London, Stephanie J.
通讯作者：
London, Stephanie J.
影响因子：
7.7
作者：
Smith, Blair H.;Campbell, Archie;Morris, Andrew D.
通讯作者：
Morris, Andrew D.
影响因子：
--
作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper
DOI：
10.1056/nejmoa1012848
发表时间：
2012-01-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Berry JD;Dyer A;Cai X;Garside DB;Ning H;Thomas A;Greenland P;Van Horn L;Tracy RP;Lloyd-Jones DM
通讯作者：
Lloyd-Jones DM
吸烟的表观遗传签名。
DOI：
10.1161/circgenetics.116.001506
发表时间：
2016-10
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
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
通讯作者：
London SJ