对喘多基因风险评分的表观基因组分区揭示了不同的遗传驱动疾病途径
Bernard Stikker1, Lianne Trap1,2,3, Bahar Sedaghati-Khayat2,3
1Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
The European respiratory journal
|June 20, 2024
概括
多基因风险评分有效预测喘,特别是儿童发作的喘. 这些遗传风险因素通过表观基因组分析与特定的喘途径联系起来,有助于个性化风险管理.
科学领域:
- 遗传学 是一个遗传学.
- 肺部病理学 肺部病理学
- 流行病学 流行病学
背景情况:
- 喘易感性有很大差异,遗传贡献及其在疾病病理生理学中的作用尚不清楚.
- 了解遗传预测因素对于个性化喘风险评估至关重要.
研究的目的:
- 开发多基因风险评分 (PRS) 用于预测喘风险.
- 通过表观基因组来将PRS识别的遗传变异与喘病理生理学联系起来.
主要方法:
- 使用来自全基因组关联研究的单核酸变体构建PRS.
- 在潜在的鹿特丹研究队列 (14,926人) 中验证了PRS.
- 利用来自19种细胞类型的全基因组染色质数据进行表观基因PRS分区.
主要成果:
- PRS准确预测了喘和相关结果,特别是儿童发作的喘 (AUC 0.760).
- 根据PRS,个人成功地被分为高风险和低风险组.
- 表观基因组分离揭示了与特定喘相关的细胞,基因和途径相关的五个变异集群.
结论:
- 在荷兰队列中,PRS与喘特征有显著的关联,对儿童发作的喘具有更高的预测能力.
- 在表观基因组上,PRS变异被聚集在一起,这表明了不同的,基因驱动的喘途径.
- 研究结果表明,有可能针对个性化喘风险减轻和治疗策略.
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