提丁缩小变体在不同人群中倾向于扩展性心肌病
John DePaolo1, Marc Bornstein2, Renae Judy1
1Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
medRxiv : the preprint server for health sciences
|January 31, 2024
概括
在 (hiPSI) TTN截断变体 (TTNtvs) 中剪接的高百分比增加了不同人群中的扩张性心肌病 (DCM) 风险. 遗传背景不会改变TTNtv对DCM的风险,支持对与titin相关的DCM进行普遍查.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 心血管疾病 心血管疾病
- 人口健康 人口健康
背景情况:
- 在 (hiPSI) TTN截断变体 (TTNtvs) 中剪接的高百分比和扩展性心肌病 (DCM) 风险之间的关联主要研究在欧洲祖先种群中.
- 关于TTNtv对不同种群的影响的数据有限,特别是那些与非洲参考种群基因相似的种群,这阻碍了全面的风险评估.
研究的目的:
- 调查TTNtvs与DCM风险在不同人群中的关联.
- 评估基因距离 (GD) 与参考种群对TTNtv相关的DCM风险的影响.
主要方法:
- 一项队列研究使用来自宾夕法尼亚大学医学生物库 (PMBB) 的数据进行,这是一个大型,多样化的生物库.
- 分析了参与者的整个外体序列数据和电子健康记录.
- 基因相似性是使用相对于1000个基因组项目参考种群的主要成分分析来评估的.
主要成果:
- 在多样化的PMBB队列中,hiPSI TTNtvs与DCM风险增加显著相关.
- 与TTNtv相关的DCM风险的影响估计在1000G欧洲中心离子基因距离的分数上保持一致.
- 在与欧洲 (OR=7.55) 和非洲 (OR=3.50) 参考种群遗传相似的子组中观察到显著的DCM风险.
结论:
- 在各种祖先背景中,TTNtvs是DCM的重要风险因素.
- 对于DCM,TTNtvs所带来的风险并没有受到基因背景的显著改变.
- 这些发现表明,遗传背景不应该成为查与titin相关的DCM的障碍.
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