对异形性肺纤维化和间歇性肺异常的多基因风险评分
Matthew Moll1,2, Anna L Peljto3,4, John S Kim5
1Division of Pulmonary and Critical Care Medicine, and.
概括
常见的遗传变异显著预测异常性肺纤维化 (IPF) 和间歇性肺异常 (ILAs). 在MUC5B区域之外的多基因风险评分 (PRS) 提高了IPF预测,有助于早期识别有风险的个体.
科学领域:
- 遗传学 遗传学 是一个
- 肺部医学 肺部医学
- 流行病学 流行病学
背景情况:
- 常见的遗传变异,以及罕见的变异和MUC5B位点,有助于异常性肺纤维化 (IPF) 风险.
- 在MUC5B区域以外的常见变异对IPF和间歇性肺异常 (ILAs) 的预测能力在很大程度上仍然未被描述.
研究的目的:
- 评估IPF多基因风险评分 (PRS) 的预测性表现,包括和不包括MUC5B区域.
- 评估PRS与IPF诊断,ILA存在和ILA进展的关联.
主要方法:
- 使用IPF全基因组关联研究数据开发两个PRS:一个包括MUC5B区域 (PRS-M5B),一个不包括MUC5B区域 (PRS-NO-M5B).
- 评估PRS的预测准确度使用接收器运行特征曲线 (AUC) 下面的面积在六个多祖先队列中的指标.
- 包括14,650名参与者,其中1,970人被诊断患有IPF,1,068人患有ILA.
主要成果:
- 无论是PRS-M5B还是PRS-NO-M5B,都显示出与IPF风险的显著关联 (每次SD的OR分别为3.1和2.8).
- 在PRS-NO-M5B中,IPF在最高五分位数的几率比最低五分位数增加了七倍.
- 结合rs35705950-T (MUC5B区域) 和PRS-NO-M5B的临床模型实现了最高的IPF预测性能 (AUC,0.81).
- 在欧洲祖先的参与者中,PRS-NO-M5B与ILA和ILA进展有关.
结论:
- 在MUC5B区域之外包含常见遗传变异的PRS显著预测IPF和ILA.
- 这种常见的遗传变异风险评分补充了MUC5B变异,用于识别患间歇性肺部疾病高风险的个体.
- 遗传风险评分为肺纤维化和相关肺部疾病风险分层提供了有价值的工具.
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