Qiu Weiliang, Wan Emily, Morrow Jarrett, Cho Michael H, Crapo James D, Silverman Edwin K, DeMeo Dawn L
a Channing Division of Network Medicine; Brigham and Women's Hospital/Harvard Medical School ; Boston , MA USA.
b Division of Pulmonary/Critical Care; Brigham and Women's Hospital/Harvard Medical School ; Boston , MA USA.
Epigenetics. 2015;10(11):1064-73. doi: 10.1080/15592294.2015.1106672.
DNA methylation can be affected by systemic exposures, such as cigarette smoking and genetic sequence variation; however, the relative impact of each on the epigenome is unknown. We aimed to assess if cigarette smoking and genetic variation are associated with overlapping or distinct sets of DNA methylation marks and pathways. We selected 85 Caucasian current and former smokers with genome-wide single nucleotide polymorphism (SNP) genotyping available from the COPDGene study. Genome-wide methylation was obtained on DNA from whole blood using the Illumina HumanMethylation27 platform. To determine the impact of local sequence variation on DNA methylation (mQTL), we examined the association between methylation and SNPs within 50 kb of each CpG site. To examine the impact of cigarette smoking on DNA methylation, we examined the differences in methylation by current cigarette smoking status. We detected 770 CpG sites annotated to 708 genes associated at an FDR < 0.05 in the cis-mQTL analysis and 1,287 CpG sites annotated to 1,242 genes, which were nominally associated in the smoking-CpG association analysis (P(unadjusted) < 0.05). Forty-three CpG sites annotated to 40 genes were associated with both SNP variation and current smoking; this overlap was not greater than that expected by chance. Our results suggest that cigarette smoking and genetic variants impact distinct sets of DNA methylation marks, the further elucidation of which may partially explain the variable susceptibility to the health effects of cigarette smoking. Ascertaining how genetic variation and systemic exposures differentially impact the human epigenome has relevance for both biomarker identification and therapeutic target development for smoking-related diseases.
DNA甲基化会受到全身暴露因素的影响，如吸烟和基因序列变异；然而，它们各自对表观基因组的相对影响尚不清楚。我们旨在评估吸烟和基因变异是否与重叠或不同的DNA甲基化标记及途径相关联。我们从慢性阻塞性肺疾病基因（COPDGene）研究中选取了85名有全基因组单核苷酸多态性（SNP）基因分型数据的白种人现吸烟者和既往吸烟者。使用Illumina HumanMethylation27平台对全血DNA进行全基因组甲基化检测。为了确定局部序列变异对DNA甲基化（mQTL）的影响，我们研究了每个CpG位点50 kb内甲基化与SNP之间的关联。为了研究吸烟对DNA甲基化的影响，我们根据当前吸烟状况研究了甲基化差异。在顺式mQTL分析中，我们检测到770个注释到708个基因的CpG位点，其错误发现率（FDR）<0.05；在吸烟与CpG关联分析中，检测到1287个注释到1242个基因的CpG位点，其名义上具有相关性（P（未校正）<0.05）。43个注释到40个基因的CpG位点与SNP变异和当前吸烟均相关；这种重叠不大于偶然预期。我们的结果表明，吸烟和基因变异影响不同的DNA甲基化标记集，对其进一步阐明可能部分解释吸烟对健康影响的易感性差异。确定基因变异和全身暴露如何不同地影响人类表观基因组对于吸烟相关疾病的生物标志物识别和治疗靶点开发都具有重要意义。
