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首页> 外文期刊>Circulation. Genomic and precision medicine. >Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians
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Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians

机译：验证的全基因组多基因风险评分在法国加拿大人冠状动脉疾病

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BACKGROUND: Coronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual's genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Two recently derived genome-wide PRS have shown high specificity and sensitivity to identify CAD cases in European-ancestry participants from the UK Biobank. However, validation of the PRS predictive power and transferability in other populations is now required to support their clinical utility. METHODS: We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from 3 cohorts totaling 3639 prevalent CAD cases and 7382 controls and tested their power to predict prevalent, incident, and recurrent CAD. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion (LDLR delta >15 kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. RESULTS: Our results confirm the ability of both PRS to predict prevalent CAD comparable to the original reports (area under the curve=0.72-0.89). Furthermore, the PRS identified about 6% to 7% of individuals at CAD risk similar to carriers of the LDLR delta >15 kb mutation, consistent with previous estimates. However, the PRS did not perform as well in predicting an incident or recurrent CAD (area under the curve=0.56-0.60), maybe because of confounding because 76% of the participants were on statin treatment. This result suggests that additional work is warranted to better understand how ascertainment biases and study design impact PRS for CAD. CONCLUSIONS: Collectively, our results confirm that novel, genomewide PRS is able to predict CAD in French Canadians; with further improvements, this is likely to pave the way towards more targeted strategies to predict and prevent CAD-related adverse events.
机译：背景:冠状动脉疾病(CAD)是发病的主要原因之一和死亡率。与CAD相关的风险和社会影响,他们的临床管理将会从中受益提高预防和预测工具。基于一个多基因风险评分(PRS)成为个人的基因组序列潜在的强大的生物标记物预测风险开发CAD。全基因组PRS显示高特异性和敏感性识别CAD的病例参与者来自英国的欧洲血统生物。预测能力和可转让性人口现在需要支持他们临床实用程序。(GPSCAD和metaGRSCAD)的法裔加拿大人个人从3组共计3639人流行CAD病例和7382控制和测试他们的权力来预测普遍、事件和复发性CAD。法裔加拿大人家族创始人高胆固醇血症删除(LDLRδ> 15 kb删除)CAD在其中一个军团和风险用这个估计校准的影响PRS。即PRS CAD与预测普遍最初的报告(面积曲线= 0.72 - -0.89)。大约6%到7%的个人风险CAD相似运营商的LDLR三角洲> 15 kb突变,与先前的估计一致。PRS不执行在预测一个事件或复发CAD(面积曲线= 0.56 - -0.60),也许是因为混杂因为76%的参与者在他汀类药物治疗。工作是保证更好的理解确定偏差和PRS研究设计的影响CAD。确认小说,全基因组PRS能够预测CAD在法国加拿大人;改进,这是可能铺平了道路对预测和更有针对性的策略防止CAD-related不良事件。

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