与电子病历记录的表型相关的基因变异的关联
Sara L Van Driest1, Quinn S Wells1, Sarah Stallings1
1Vanderbilt University Medical Center, Nashville, Tennessee.
JAMA
|January 10, 2016
概括
在11%的个体中发现了SCN5A和KCNH2不律性基因的罕见变异. 然而,这些遗传变异在本研究群体中没有与心律失常表型的明显关联.
科学领域:
- 遗传学
- 心脏病学
- 药物基因组学
背景情况:
- 大规模的DNA测序经常识别孟德尔病基因的罕见变异.
- 这些偶然发现在未经选择的群体中的临床意义尚不清楚.
- 电子病历 (EMR) 为评估与罕见变异相关的临床表型提供了潜在的资源.
研究的目的:
- 调查与心律失常易感基因 (SCN5A和KCNH2) 的致病变异相关的临床表型.
- 使用EMR数据确定携带这些变体的个体心脏表型的频率.
主要方法:
- 对2022个人的前性队列研究进行.
- 专家实验室和ClinVar对SCN5A和KCNH2的变体进行了病原性评估.
- 通过ICD-9代码,心电图数据和手动EMR审查来确定表型.
主要成果:
- 11% 的参与者携带罕见的SCN5A或KCNH2变异.
- 63个人的42个变体被认为是潜在的病原体,实验室间一致性较低.
- 携带这些变体和心律失常或心电图表型之间没有发现显著的关联,包括纠正的QT间隔持续时间.
结论:
- 实验室对SCN5A和KCNH2变体的病原性分类一致性较低.
- 这些心律失常基因的潜在致病基因变异与未经选择的人群中的异常表型无关.
- 这些发现挑战了通知患者发生心律失常的偶然遗传发现的临床有用性.
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