Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University.
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University.
Curr Opin Lipidol. 2019 Apr;30(2):71-81. doi: 10.1097/MOL.0000000000000576.
With improved next-generation sequencing technology, open-access genetic databases and increased awareness of complex trait genetics, we are entering a new era of risk assessment in which genetic-based risk scores (GRSs) will play a clinical role. We review the concepts underlying polygenic models of disease susceptibility and challenges in clinical implementation.
Polygenic risk scores are currently used in genetic research on dyslipidemias and cardiovascular disease (CVD). Although the underlying principles for constructing polygenic scores for lipids are established, the lack of consensus on which score to use is indicated by the large number - about 50 - that have been published. Recently, large-scale polygenic scores for CVD appear to afford superior risk prediction compared to small-scale scores. Despite the potential benefits of GRSs, certain biases towards ethnicity and sex need to be worked through.
We are on the verge of clinical application of GRSs to provide incremental information on dyslipidemia and CVD risk above and beyond traditional clinical variables. Additional work is required to develop a consensus of how such scores will be constructed and measured in a validated manner, as well as clinical indications for their use.
随着下一代测序技术、开放获取的遗传数据库以及对复杂性状遗传学认识的提高，我们正进入一个新的风险评估时代，遗传风险评分（GRS）将发挥临床作用。我们回顾了疾病易感性多基因模型的概念以及临床实施中的挑战。
多基因风险评分目前用于血脂异常和心血管疾病（CVD）的遗传研究。虽然已经确定了构建脂质多基因评分的基本原则，但已经发表了大约 50 个评分，这表明缺乏使用哪种评分的共识。最近，大规模 CVD 多基因评分似乎比小规模评分提供了更好的风险预测。尽管 GRS 具有潜在的益处，但需要解决某些种族和性别偏见。
我们即将将 GRS 应用于临床，以提供血脂异常和 CVD 风险的额外信息，这些信息超过了传统的临床变量。需要进一步开展工作，以达成共识，以验证的方式构建和衡量此类评分，并确定其使用的临床适应证。
