一个整合的分子风险得分在生命早期,以后的童年喘风险
Andreas Böck1,2, Kathrin Urner1,2, Jana Kristin Eckert1,2
1Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
概括
预测儿童喘对于早期干预至关重要. 虽然分子标记剂提供了适度的改善,但结合出生风险因素和以后的过敏症状显著提高了预测的准确性.
科学领域:
- 儿科过敏和免疫学
- 遗传学和基因组学 遗传学和基因组学
- 流行病学 流行病学
背景情况:
- 儿童喘影响了早期喘息的儿童的重要亚组.
- 早期识别有风险的儿童对于及时管理和预防严重后果至关重要.
- 整合遗传和临床数据有助于预测儿童喘发展.
研究的目的:
- 开发一个综合风险评分来预测儿童喘.
- 结合已确定的风险因素,出生时的全基因组分子标记物和随后的临床症状,以改善预测.
主要方法:
- 利用了三个纵向出生队列 (PAULINA/PAULCHEN, PASTURE) 的流行病学和分子数据 (基因型,DNA甲基化,mRNA表达).
- 使用的纳伊夫-贝叶斯和拉索回归模型用于明显和乐观度纠正的绩效评估 (AUC/R2).
- 在PASTURE队列中分析了从带血到6岁的纵向mRNA表达变化.
主要成果:
- 出生时的流行病学因素预测了喘,乐观度校正的AUC (ocAUC) 为0.65.
- 分子标志物适度改善了预测 (ocAUC高达0.68).
- 包括早期的过敏症状/诊断显著提高了预测能力 (ocAUC高达0.76).
- 六岁时的纵向mRNA表达显示出与喘的最强相关性,随着时间的推移,基因相关性增加.
结论:
- 仅仅流行病学预测因素就提供了中度喘预测.
- 出生时的分子标志物为预测模型提供了适度的增强.
- 过敏症状/诊断是关键预测因素,为临床应用和未来研究显著改善模型性能.
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