Genomics plc, Oxford, United Kingdom (F.R.-M., M.E.W., R.M., S.S., E.K., R.M.S., W.A.T., P.S., A.S.L., J.A.G., A.S., C.C.A.S., V.P., P.D.).
Institute of Cardiovascular Sciences, University College London, United Kingdom (J.D.).
Circ Genom Precis Med. 2021 Apr;14(2):e003304. doi: 10.1161/CIRCGEN.120.003304. Epub 2021 Mar 2.
There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment.
Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals.
The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7-7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%-15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6-19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period.
An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person's polygenic risk.
人们对于是否可以利用遗传数据来改进标准心血管疾病风险计算器很感兴趣，因为后者通常用于临床实践来管理预防性治疗。
我们利用英国生物库资源，为冠心病（CAD）开发了自己的多基因风险评分。我们使用英国生物库中的另外 60000 人开发了一个综合风险工具（IRT），该工具将我们的多基因风险评分与已建立的风险工具（美国心脏协会/美国心脏病学会 pooled cohort equations [PCE]或 UK QRISK3）相结合，并用英国生物库中的另外 186451 人对我们的 IRT 进行了测试。
与其他已发表的多基因风险评分相比，新型 CAD 多基因风险评分对 CAD 事件具有更高的预测能力，且与 PCE 和 QRISK3 相关性不大。当与 PCE 结合形成 IRT 时，它具有更高的预测准确性。总体而言，10.4%的新发 CAD 病例被 PCE 错误归类为低风险，而被 IRT 正确归类为高风险，而 4.4%的病例被 IRT 错误归类为低风险，被 PCE 正确归类为高风险。IRT 的总体净重新分类改善率为 5.9%（95%CI，4.7-7.0）。当按年龄和性别亚组分层时，所有亚组的改善幅度都较大（范围为 8.3%-15.4%），40-54 岁男性的效果最佳（15.4%[95%CI，11.6-19.3]）。使用不同的风险工具（QRISK3）和更广泛的心血管疾病定义也得到了类似的结果。使用 IRT 估计可在美国避免多达 12000 人在 5 年内死亡。
纳入多基因风险的 IRT 优于当前的风险分层工具，并为早期干预提供了更大的机会。鉴于基因检测成本的大幅下降，未来的 CAD 风险工具迭代将通过添加个人的多基因风险得到增强。
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