Department of Bioengineering.
Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, California, USA.
Curr Opin Cardiol. 2019 Jul;34(4):435-440. doi: 10.1097/HCO.0000000000000629.
Large genome-wide association studies (GWAS) have identified variants accounting for a substantial portion of the heritable risk for coronary artery disease (CAD). These studies have catalyzed drug discovery and generated the possibility of improved risk prediction and stratification. Here, we review the current state-of-the art in polygenic risk scores (PRSs) and look to the future, as these scores move towards clinical application.
Over the last decade, multilocus PRSs for CAD have expanded to include millions of variants and demonstrated strong association with CAD outcomes, even when adjusted for traditional risk factors. Recently, PRSs have shown better prediction of CAD outcomes than any single traditional risk factor alone. Advances in statistical methods used to generate PRSs have improved their predictive ability and transferability between populations with varied ancestries. Initial clinical studies have also demonstrated the potential of genetic information to impact shared decision-making between patients and providers, leading to improved outcomes.
PRSs can improve risk stratification for CAD especially in white/European populations and have the potential to alter routine clinical care. However, unlocking this potential will require additional research in PRSs in nonwhite populations and substantial investment in clinical implementation studies.
全基因组关联研究（GWAS）已经确定了许多变体，这些变体可以解释冠心病（CAD）遗传风险的很大一部分。这些研究促进了药物发现，并为改善风险预测和分层提供了可能。在这里，我们回顾多基因风险评分（PRSs）的最新进展，并展望未来，因为这些评分正在向临床应用发展。
在过去的十年中，用于 CAD 的多基因 PRS 已经扩展到包含数百万个变体，并证明与 CAD 结果有很强的关联，即使在调整了传统危险因素后也是如此。最近，PRSs 显示出比任何单一传统危险因素更好的 CAD 结果预测能力。用于生成 PRS 的统计方法的进步提高了它们在具有不同祖源的人群之间的预测能力和可转移性。初步的临床研究也表明，遗传信息有可能影响患者和提供者之间的共同决策，从而改善结果。
PRSs 可以改善 CAD 的风险分层，特别是在白种/欧洲人群中，并且有可能改变常规的临床护理。然而，要实现这一潜力，需要在非白人群体中进行 PRS 的进一步研究，并在临床实施研究中进行大量投资。
