冠心病多部位遗传风险评分:病例控制和前性队列分析
Samuli Ripatti1, Emmi Tikkanen, Marju Orho-Melander
1Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. samuli.ripatti@fi mm.fi
Lancet (London, England)
|October 26, 2010
概括
使用13个单核酸多态 (SNP) 的遗传风险评分可以识别患冠心病 (CHD) 风险较高的个体. 这一分数有助于确定20%的欧洲血统个体有70%的首次CHD事件风险增加.
科学领域:
- 心血管遗传学 心血管遗传学
- 基因组学就是基因组学.
- 流行病学 流行病学
背景情况:
- 全基因组关联研究 (GWAS) 确定了与冠心病 (CHD) 相关的单核酸多态 (SNP).
- 对这些SNP发现的外部验证对于精确的风险评估至关重要.
- 前性队列研究为验证遗传关联提供了强大的设计.
研究的目的:
- 为了验证13个最近发现的SNP与CHD相关.
- 使用独立队列来建立外部有效性.
- 使用遗传风险得分 (GRS) 估计心脏病风险.
主要方法:
- 在病例控制和前性队列设计中测试了13个SNP.
- 参与者:3829例心血管疾病病例,48,897例对照病例,30,725例无病患者.
- 模拟了多位基因风险评分 (GRS);使用了Cox比例危险和后勤回归.
主要成果:
- 在前性队列分析中,GRS与第一个CHD事件相关.
- 在GRS的顶级五分之一中,CHD风险增加了1.66倍 (根据传统因素进行调整).
- 在综合歧视指数上,GRS显示出很小的影响,但没有显著改善C指数或净重新分类.
结论:
- 对13个CHD相关SNP的GRS识别出20%的欧洲血统个体有~70%的风险增加.
- 这种遗传面板的临床实用性需要进一步定义.
- 遗传风险分层可能有助于个性化心血管疾病预防策略.
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