基于文献的遗传风险评分与女性心血管事件之间的关联
Nina P Paynter1, Daniel I Chasman, Guillaume Paré
1Center for Cardiovascular Disease Prevention and the Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. npaynter@partners.org
JAMA
|February 18, 2010
概括
使用101个遗传标记的遗传风险评分在考虑传统风险因素后,无法预测女性的心血管疾病. 家庭病史仍然是心脏病风险的重要预测因素.
科学领域:
- 心血管疾病遗传学 心血管疾病遗传学
- 流行病学 流行病学
- 生物标志物 生物标志物
背景情况:
- 全基因组关联研究 (GWAS) 已经确定了心血管疾病 (CVD) 的众多遗传标记.
- 除了已确定的因素之外,这些遗传标记对心血管疾病风险的累积影响仍然不清楚,特别是在女性中.
研究的目的:
- 评估发生心血管疾病的遗传风险评分 (GRS) 的预测能力.
- 评估GRS是否能改善风险预测,当与传统的心血管疾病风险因素相结合时.
主要方法:
- 针对19313名最初健康的白人女性进行了前性队列研究 (女性基因组健康研究).
- 使用101个与心血管疾病或其表型相关的单核酸多态 (SNPs) 开发了一个GRS (P < 10(-7).
- 参与者被跟踪了12.3年的中位数,主要的不良心血管事件 (MACE).
主要成果:
- 在年龄调整后,GRS显示了与心血管疾病风险的适度关联 (HR 1.02 每个等位基因,P = .006).
- 然而,经过传统风险因素 (如胆固醇,血压) 的调整后,GRS并没有显著改善心血管疾病风险歧视或重新分类 (净重新分类改善0.5%,P = .24).
- 自我报告的心血管疾病家族史在多变量模型中仍然是一个重要的预测因素,与GRS不同.
结论:
- 当考虑传统的风险因素时,由101个SNP组成的GRS并没有显著改善最初健康妇女的心血管疾病风险预测.
- 传统的心血管风险因素和家族病史在风险分层方面似乎比这个队列中测试的多基因风险得分更为关键.
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