使用结构化电子健康记录数据进行基于外体的基因型-第一个反向表型识别,识别了与肝脏标志物相关的新型SERPINA1变异,并证明了特定变异对肝脏表型具有主导作用
Maël Silva Rodriguez1,2, Margaux Mulot1, Céline Chéry1,2,3
1Department of Genomic Medicine, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, Nancy, France.
概括
这项研究使用了基因型第一方法来识别与肝脏疾病相关的SERPINA1变异. 研究结果揭示了新的基因型-生物标志物联系,支持对无法解释的肝脏疾病进行遗传测试.
科学领域:
- 遗传学 是一个遗传学.
- 肝病学 肝病学是一种肝病学.
- 生物标志物发现发现
背景情况:
- 以表型为驱动的方法已经确定了致病性SERPINA1变体,导致肝脏疾病.
- 缺少对SERPINA1位点的基因型驱动研究.
- 对患有非良性SERPINA1变异的患者的临床和生物概况的描述至关重要.
研究的目的:
- 通过基因型优先方法来描述患有非良性SERPINA1变异患者的临床和肝脏生物概况.
- 在SERPINA1位点内识别新的基因型-生物标志物关联.
- 评估SERPINA1基因测试在患有不明原因肝脏异常的患者中的有用性.
主要方法:
- 追溯性,基于外体的,基因型-首先反向表型化研究.
- 利用了2015年1月至2022年1月的电子健康记录数据.
- 使用频率主义和贝叶斯模型评估的统计学关联,在英国生物银行队列中得到验证.
主要成果:
- 在1377名患者 (15.7%) 中,在217名患者中发现了15种非良性SERPINA1变异.
- 在分析的患者中观察到的肝病 (32.5%),高血症 (23%),肺气 (5.6%).
- 确认了已知的变异关联,并确定了三个新的基因型-生物标志物关联 (c.*10G>A,c.1065+10C>T,p.Arg63Cys).
结论:
- 基因型为首的方法是有效的,用于表征非良性SERPINA1变异的肝脏表现.
- 发现了新的基因型-生物标志物关联.
- SERPINA1基因测试可能有助于诊断无法解释的肝脏异常.
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