Transcriptomic epidemiology of smoking: the effect of smoking on gene expression in lymphocytes
Transcriptomic epidemiology of smoking: the effect of smoking on gene expression in lymphocytes
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DOI：
10.1186/1755-8794-3-29
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发表时间：
2010-07-15
影响因子：
2.7
通讯作者：
Blangero, John
中科院分区：
文献类型：
--
作者：
Charlesworth, Jac C.;Curran, Joanne E.;Blangero, John
背景资料：这项调查提供了深入了解全系统的病理过程中诱导响应香烟烟雾暴露，通过确定其在基因expression level.Methods的影响：我们获得了全基因组的定量转录谱从1,240个人的圣安东尼奥家庭心脏研究，包括297个当前吸烟者。使用淋巴细胞样本，我们确定了20，413个具有显著可检测表达水平的转录本，包括已知和预测的基因。吸烟和基因表达水平之间的相关性，使用回归模型，允许残留的遗传effects.Results：与保守的错误发现率为5%，我们确定了323个独特的基因（342转录），其表达水平与吸烟behaviors. Results显着相关。这些基因表现出显着的过度代表性的范围内的功能类别，以及与已知的吸烟相关的病理学，包括免疫反应，细胞死亡，癌症，自然杀伤细胞信号和异生素metabolization.Conclusions：我们的研究结果表明，不仅个别基因，但整个网络的基因相互作用的影响，吸烟。这是迄今为止规模最大的吸烟体内转录组流行病学研究，揭示了香烟烟雾作为环境变量对基因表达的重大而全面的影响。这份手稿的核心重要性是提供一个总结的基因表达和吸烟之间的关系，在这个异常大的横截面数据集。
Background: This investigation offers insights into system-wide pathological processes induced in response to cigarette smoke exposure by determining its influences at the gene expression level.Methods: We obtained genome-wide quantitative transcriptional profiles from 1,240 individuals from the San Antonio Family Heart Study, including 297 current smokers. Using lymphocyte samples, we identified 20,413 transcripts with significantly detectable expression levels, including both known and predicted genes. Correlation between smoking and gene expression levels was determined using a regression model that allows for residual genetic effects.Results: With a conservative false-discovery rate of 5% we identified 323 unique genes (342 transcripts) whose expression levels were significantly correlated with smoking behavior. These genes showed significant over-representation within a range of functional categories that correspond well with known smoking-related pathologies, including immune response, cell death, cancer, natural killer cell signaling and xenobiotic metabolism.Conclusions: Our results indicate that not only individual genes but entire networks of gene interaction are influenced by cigarette smoking. This is the largest in vivo transcriptomic epidemiological study of smoking to date and reveals the significant and comprehensive influence of cigarette smoke, as an environmental variable, on the expression of genes. The central importance of this manuscript is to provide a summary of the relationships between gene expression and smoking in this exceptionally large cross-sectional data set.