新生儿 DNA 甲基化、儿童期肺功能与一生中哮喘和 COPD 的发病风险。
Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course.
机构信息
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Dept of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
出版信息
Eur Respir J. 2019 Apr 4;53(4). doi: 10.1183/13993003.01795-2018. Print 2019 Apr.
RATIONALE
We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.
METHODS
We meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV), FEV/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.
RESULTS
We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were , , , , , , , , and . Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.
INTERPRETATION
Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.
背景
我们旨在确定与儿童肺功能、哮喘和慢性阻塞性肺疾病（COPD）相关的脐带血 DNA 中差异甲基化区域（DMR）。
方法
我们对五个队列的 1688 名儿童的全基因组表观遗传数据进行了荟萃分析，以确定脐带血 DMR 及其注释基因与 7-13 岁时的 1 秒用力呼气量（FEV）、FEV/用力肺活量（FVC）比值和 FVC 的 75%用力呼出流量之间的关系。鉴定的 DMRs 被探索与儿童哮喘、成人肺功能和 COPD、基因表达和参与生物学过程的关系。
结果
我们确定了 59 个与儿童肺功能相关的 DMR，其中 18 个与儿童哮喘有关，9 个与成年后 COPD 有关。鉴定的前 10 个 DMR 注释的基因包括、、、、、、、、和。在儿童期和成年期分别观察到 32 个和 18 个 DMR 的差异基因表达。与 16 个已识别 DMR 相关的基因与呼吸发育或致病途径有关。
结论
我们的研究结果表明，新生儿的表观遗传状态会影响生命过程中的呼吸道健康和疾病。
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