多基因风险评分和深静脉血栓形成的风险分层
Valeria Lo Faro1, Therese Johansson2, Julia Höglund1
1Department of Immunology, Genetics and Pathology, Genomics and Neurobiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Thrombosis research
|June 18, 2023
概括
遗传因素显著影响深静脉血栓塞 (DVT) 的风险. 这项研究确定了新的遗传变异,并开发了多基因风险评分 (PRS) 来改善DVT预测,强调了个性化预防策略对具有高遗传倾向的个体的好处.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 心血管医学 心血管医学
- 生物信息学是一种生物信息学.
背景情况:
- 深静脉血栓症 (DVT) 是一种复杂的疾病,具有显著的遗传贡献,大约60%的风险归因于诸如V莱登因子 (FVL) 等因素.
- 目前的DVT预防策略存在研究缺口,需要改进风险预测模型.
- 严重心血管梗塞经常表现出非特异性症状,延迟诊断和治疗,如果不治疗,可能导致严重的并发症.
研究的目的:
- 描述对DVT的遗传贡献,并评估遗传构成对风险预测的影响.
- 为了识别与DVT风险相关的新型遗传变异.
- 评估多基因风险评分 (PRS) 对预测DVT风险的有用性,包括它们在具有和没有已知的致病变体 (如FVL) 的表现.
主要方法:
- 利用英国生物库 (UKB) 的外基因组测序和全基因组关联研究数据进行基因关联测试.
- 在一个庞大的队列子组 (8,231例,276,360对照) 中构建了多基因风险得分 (PRS).
- 在单独的队列中验证了PRS预测能力 (4,342例,142,822对照) 和生成的PRS,不包括已知的致病变体.
主要成果:
- 发现并复制了一种新的常见变异 (rs11604583) 和一种与增加DVT风险 (2.5倍) 相关的罕见变异 (rs187725533).
- 在PRS的上十分位数中,DVT风险增加了3.4倍,当排除FVL载体时,该风险增加了2.3倍.
- 在顶级PRS十分位数中,80岁时DVT累积风险为FVL携带者10%而非携带者为5%,高多基因风险占该队列DVT病例的20%左右.
结论:
- 具有高多基性DVT风险的个体,除了携带诸如FVL之类的众所周知的变体之外,可以从有针对性的预防策略中受益.
- 基因分析和PRS为个性化DVT风险评估和预防提供了一个有希望的途径.
- 对遗传因素的进一步研究可以帮助缩小DVT预防研究差距,并改善患者的治疗结果.
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