罕见和常见的基因变异是心房的潜在风险
Oliver B Vad1,2, Laia M Monfort1,2, Christian Paludan-Müller1,2
1Department of Cardiology, The Heart Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
JAMA cardiology
|June 26, 2024
概括
罕见的遗传变异和多基因风险得分显著增加了心房动 (AF) 的风险. 这些发现提高了对AF遗传学的理解,并可能改善这种常见心脏病的风险分层.
科学领域:
- 心血管遗传学 心血管遗传学
- 失律症的遗传学 失律症的遗传学
- 基因组流行病学 基因组流行病学
背景情况:
- 心房动 (AF) 具有显著的遗传基础,多基因风险已得到证实.
- 罕见遗传变异在AF易感性中的作用需要在大量人群中进一步研究.
研究的目的:
- 为了确定与AF相关的罕见预测功能丧失 (pLOF) 变体.
- 评估罕见变异和多基因风险评分 (PRS) 对AF,心肌病 (CM) 和心力衰竭 (HF) 风险的综合影响.
主要方法:
- 一项基因关联和嵌套病例对照研究,利用英国生物库数据 (n=403,990).
- 对罕见的pLOF变体与发生的AF,CM和HF相关的评估.
- 具体原因的考克斯回归模型用于风险评估.
主要成果:
- 六个基因 (TTN,RPL3L,PKP2,CTNNA3,KDM5B,C10orf71) 的罕见pLOF变异与AF有关,其中五个在外部队列中复制.
- 罕见的pLOF变体和高PRS的组合显著增加了AF风险 (OR,7.08).
- 具有罕见pLOF变异的高PRS携带者表现出相当大的10年AF风险 (16%的女性,24%的男性>60岁) 和增加CM风险的AF前后诊断.
结论:
- 罕见和常见的遗传变异都会增加AF风险.
- 这些发现为AF的遗传结构提供了有价值的见解.
- 这项研究表明,有可能改善AF的遗传风险分层策略.
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