致病性/可能致病性遗传性心肌病变体与心力衰竭的关联:TOPMed多祖先分析
Naman S Shetty1, Mokshad Gaonkar2, Akhil Pampana2
1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Mayo Clinic proceedings
|August 23, 2025
概括
大约每140名成年人中就有1名携带遗传性心肌病变体,增加心力衰竭的风险. 基因查可以确定早期干预的携带者,并减少心力衰竭的发生率.
科学领域:
- 遗传学
- 心脏病学
- 精准医学
背景情况:
- 遗传性心肌病是导致心力衰竭的重要原因.
- 遗传变异在这些疾病的发展中起着至关重要的作用.
- 了解这些变种的流行和影响对于公共卫生至关重要.
研究的目的:
- 确定致病性/可能致病性遗传性心肌病变体在TransOmic for Precision of Medicine (TOPMed) 队列中的患病率.
- 评估携带这些变体与患心力衰竭的风险之间的关联.
主要方法:
- 使用多个祖先的美国成年人的TOPMed数据进行了回顾性队列研究.
- 使用ClinVar分类确定了致病性/ 可能致病性遗传性心肌病变体的载体状态.
- 使用Cox比例危险模型分析携带者状态与心力衰竭风险之间的关联,调整为共变量.
主要成果:
- 在30977名参与者中,0. 7% (229人) 被确定为致病性/可能致病性遗传性心肌病变体的携带者.
- 心力衰竭发病率较高的变体携带者 (每1000人/ 年2. 06) 与非携带者 (每1000人/ 年1. 40) 相比.
- 携带这些变体与心力衰竭风险增加1. 68倍有关 (aHR,1. 68;95% CI,1. 29-22).
结论:
- 大约每140名美国成年人中就有1人患有心肌病变体,这显著增加了心力衰竭的风险.
- 建议通过有针对性的基因查及早识别携带者.
- 对携带者的预防性干预可能会减少心力衰竭的发生率.
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