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, USA.
American journal of human genetics
|July 4, 2025
概括
遗传变异显著影响与喘内型相关的DNA甲基化 (DNAm) 签名. 这些在出生时存在的表观遗传特征与环境因素相互作用,塑造喘发展和过敏疾病风险.
科学领域:
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 免疫学 免疫学 免疫学
- 环境健康 环境健康
背景情况:
- 喘在内型中表现出显著的异质性,遗传和环境因素的贡献不清楚.
- 了解遗传学,表观遗传学和环境之间的相互作用,对于破译喘病原体至关重要.
- 以前的研究还没有完全阐明遗传和环境影响对不同喘内型的相对影响.
研究的目的:
- 为了识别与喘表型和内型相关的DNA甲基化 (DNAm) 签名.
- 为了调查这些已识别的DNAm签名的遗传贡献.
- 探索生命早期遗传敏感性在调解童年喘中对环境暴露的表观遗传反应中的作用.
主要方法:
- 利用了城市环境和儿童喘 (URECA) 队列中的284名儿童的鼻粘膜DNA甲基化 (DNAm) 和基因表达数据.
- 在37,256个CPG上采用经验贝叶斯因子分解来识别与过敏性疾病,敏感化和2型炎症表型相关的DNAm签名.
- 在婴儿肺部感染和喘敏感性 (INSPIRE) 和儿童呼吸环境工作组 (CREW) 队列中重复发现,分析基因型数据以估计遗传性.
主要成果:
- 确定了三种与过敏性喘,过敏性鼻炎,亚托皮和2型炎症标志物 (FeNO,乙酸蛋白) 相关的不同的DNAm签名.
- 这些特征与反映关键喘内型的基因相关:对微生物的免疫反应受损,表皮屏障受损和2型免疫活性.
- 对DNAm特征的显著遗传性估计 (0.17-0.26) 表明,对潜在的过敏表型的表观遗传特征有相当大的遗传贡献.
结论:
- 遗传变异在塑造与喘中的过敏表型相关的表观遗传特征方面发挥着重要作用.
- DNAm签名的遗传性表明,对特定喘内型的遗传敏感性在出生时就存在.
- 这些发现强调了早期遗传倾向可能影响对环境暴露的表观遗传反应,从而影响喘的发展.
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