对儿童过敏现象的表观遗传定义的内型的遗传贡献
Emma E Thompson1, Xiaoyuan Zhong1, Peter Carbonetto1
1Department of Human Genetics, University of Chicago, Chicago IL.
medRxiv : the preprint server for health sciences
|March 4, 2025
概括
这项研究确定了三种与儿童喘和过敏有关的DNA甲基化特征. 呼吸道细胞中的这些表观遗传模式揭示了导致这些常见呼吸道疾病的生物过程.
科学领域:
- 遗传学和表观遗传学
- 儿科呼吸系统医学 儿科呼吸系统医学
- 免疫学 免疫学 免疫学
背景情况:
- 儿童喘是一种常见的慢性呼吸道疾病,遗传基础不明.
- 关于儿童特定喘内型的遗传贡献存在研究缺口.
- 这项研究调查了从出生起具有详细表型的儿童的甲基组,转录组和基因组.
研究的目的:
- 为了识别与儿童喘和过敏内型相关的DNA甲基化 (DNAm) 签名.
- 探索表观遗传模式,基因表达和临床表型之间的关系.
- 为了确定已识别的DNAm签名的遗传性.
主要方法:
- 在URECA出生队列中的284名儿童的鼻腔粘膜细胞上进行了DNA甲基化和RNA测序.
- 经验贝叶斯矩阵分解确定了16个DNAm签名.
- 签名,表型和基因表达之间的关联被测试并在额外的队列中复制. 使用SNP数据估计了遗传性.
主要成果:
- 三个DNAm签名与喘和与过敏相关的表型 (过敏性喘,鼻炎,亚托皮,IgE,氧化,乙氨基) 有显著的关联.
- 相关基因在免疫反应,上皮屏障和T2免疫通路中得到了丰富.
- 在两个队列中的复制证实了签名-表型关联,具有显著的遗传性估计 (0.17,0.30,0.16).
结论:
- 确定了三种遗传DNAm签名,定义了喘和过敏的内型.
- 呼吸道细胞中的表观遗传模式反映了儿童喘和过敏发展至关重要的生物过程.
- 这些发现强调了表观遗传学在儿科过敏呼吸道疾病的病因学中的作用.
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