Philibert Robert, Hollenbeck Nancy, Andersen Eleanor, Osborn Terry, Gerrard Meg, Gibbons Frederick X, Wang Kai
Department of Psychiatry, University of Iowa, Iowa City, IA USA ; Behavioral Diagnostics, Iowa City, IA USA.
Department of Psychiatry, University of Iowa, Iowa City, IA USA.
Front Psychol. 2015 Jun 2;6:656. doi: 10.3389/fpsyg.2015.00656. eCollection 2015.
Smoking is the largest preventable cause of morbidity and mortality in the world. Despite the development of numerous preventive and treatment interventions, the rate of daily smoking in the United States is still approximately 22%. Effective psychosocial interventions and pharmacologic agents exist for the prevention and treatment of smoking. Unfortunately, both approaches are hindered by our inability to accurately quantify amount of cigarette consumption from the point of initial experimentation to the point of total dependency. Recently, we and others have demonstrated that smoking is associated with genome-wide changes in DNA methylation. However, whether this advance in basic science can be employed as a reliable assay that is useful for clinical diagnosis and treatment has not been shown. In this communication, we determine the sensitivity and specificity of five of the most consistently replicated CpG loci with respect to smoking status using data from a publically available dataset. We show that methylation status at a CpG locus in the aryl hydrocarbon receptor repressor, cg05575921, is both sensitive and specific for smoking status in adults with a receiver operated curve characteristic area under the curve of 0.99. Given recent demonstrations that methylation at this locus reflects both intensity of smoking and the degree of smoking cessation, we conclude that a methylation-based diagnostic at this locus could have a prominent role in understanding the impact of new products, such as e-cigarettes on initiation of cigarette smoking among adolescents, while improving the prevention and treatment of smoking, and smoking related disorders.
吸烟是全球可预防的发病和死亡的最大原因。尽管已开发出众多预防和治疗干预措施,但美国的每日吸烟率仍约为22%。存在有效的心理社会干预措施和药物用于预防和治疗吸烟。不幸的是,从最初尝试吸烟到完全成瘾,我们都无法准确量化香烟消费量,这两种方法都受到了阻碍。最近,我们和其他人已经证明,吸烟与全基因组DNA甲基化变化有关。然而,基础科学的这一进展能否用作可靠的检测方法用于临床诊断和治疗尚未得到证实。在本通讯中,我们使用公开可用数据集的数据,确定了五个最一致重复的CpG位点相对于吸烟状态的敏感性和特异性。我们表明,芳烃受体阻遏物中一个CpG位点(cg05575921)的甲基化状态对成年人的吸烟状态既敏感又特异,受试者操作曲线下面积为0.99。鉴于最近的研究表明该位点的甲基化既反映吸烟强度又反映戒烟程度,我们得出结论,基于该位点甲基化的诊断在理解电子烟等新产品对青少年开始吸烟的影响方面可能发挥重要作用,同时改善吸烟及吸烟相关疾病的预防和治疗。