DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection.
DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection.
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DOI：
10.1186/s13073-015-0213-8
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发表时间：
2015-08-21
期刊：
影响因子：
12.3
通讯作者：
Karmaus W
中科院分区：
文献类型：
--
作者：
Everson TM;Lyons G;Zhang H;Soto-Ramírez N;Lockett GA;Patil VK;Merid SK;Söderhäll C;Melén E;Holloway JW;Arshad SH;Karmaus W
变态反应性疾病的发病率在世界范围内不断增加，强调了阐明其发病机制的必要性。本研究的目的是使用两阶段设计来确定与特应性和高血清免疫球蛋白E（IgE）相关的基因组中胞嘧啶-磷酸-鸟嘌呤（CpG）位点的DNA甲基化水平，然后在一个独立的队列中复制我们的发现。通过皮肤点刺试验和高血清IgE评估特应性。使用Illumina Infinium HumanMethylation 450 BeadChip测量来自怀特岛出生队列中18岁女性（n = 245）和男性（n = 122）的全血的甲基化水平。在数据清理和处理并去除可能具有单核苷酸多态性的探针后，对来自245名女性的254，460个CpG位点的DNA甲基化水平进行第1阶段的递归随机森林特征选择。在第2阶段，通过逻辑回归对从第1阶段选择的位点与特应性和高IgE水平（>200 kU/L）的关联进行测试，所述逻辑回归针对预测的细胞类型比例和性别进行调整。在独立的瑞典出生队列BAMSE（n = 464）中，与第2阶段的特应性显著相关的位点进行了复制试验。在第1阶段，选择了62个位点，其中22个与第2阶段的特应性相关（P值范围为6.5E−9至1.4E−5），12个与高IgE水平相关（P值范围为1.1E−5至7.1E−4），Bonferroni校正α（0.05/62 = 0.0008）。在19个可用的地点中，有13个已得到复制。我们确定了13个与特应性和高IgE相关的新表观遗传基因座，可作为未来研究的候选基因座;其中4个基因在免疫应答中具有已知作用（ZFPM 1体内的cg 04983687，PRG 2 5′UTR中的cg 18219873，EPX 3′UTR中的cg 27469152和COPA体内的cg 09332506）。本文的在线版本（doi：10.1186/s13073-015-0213-8）包含补充材料，可供授权用户使用。
The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine–phosphate–guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort. Atopy was assessed via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort. After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1. The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex. Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464). In stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E−9 to 1.4E−5) and 12 associated with high IgE levels (P-value range 1.1E−5 to 7.1E−4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available sites, 13 were replicated. We identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5′UTR of PRG2, cg27469152 in the 3′UTR of EPX, and cg09332506 in the body of COPA). The online version of this article (doi:10.1186/s13073-015-0213-8) contains supplementary material, which is available to authorized users.