Beaney Katherine E, Cooper Jackie A, Drenos Fotios, Humphries Steve E
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Clin Chem Lab Med. 2017 Aug 28;55(10):1605-1613. doi: 10.1515/cclm-2016-0984.
Risk prediction algorithms for coronary heart disease (CHD) are recommended for clinical use. However, their predictive ability remains modest and the inclusion of genetic risk may improve their performance.
QRISK2 was used to assess CHD risk using conventional risk factors (CRFs). The performance of a 19 single nucleotide polymorphism (SNP) gene score (GS) for CHD including variants identified by genome-wide association study and candidate gene studies (weighted using the results from the CARDIoGRAMplusC4D meta-analysis) was assessed using the second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases). To improve the GS, five SNPs with weak evidence of an association with CHD were removed and replaced with seven robustly associated SNPs - giving a 21-SNP GS.
The weighted 19 SNP GS was associated with lipid traits (p<0.05) and CHD after adjustment for CRFs, (OR=1.31 per standard deviation, p=0.03). Addition of the 19 SNP GS to QRISK2 showed improved discrimination (area under the receiver operator characteristic curve 0.68 vs. 0.70 p=0.02), a positive net reclassification index (0.07, p=0.04) compared to QRISK2 alone and maintained good calibration (p=0.17). The 21-SNP GS was also associated with CHD after adjustment for CRFs (OR=1.39 per standard deviation, 1.42×10-3), but the combined QRISK2 plus GS score was poorly calibrated (p=0.03) and showed no improvement in discrimination (p=0.55) or reclassification (p=0.10) compared to QRISK2 alone.
The 19-SNP GS is robustly associated with CHD and showed potential clinical utility in the UK population.
冠心病（CHD）风险预测算法被推荐用于临床。然而，它们的预测能力仍然有限，纳入遗传风险可能会提高其性能。
使用QRISK2通过传统风险因素（CRFs）评估冠心病风险。使用第二项诺斯威克公园心脏研究（NPHSII）对2775名健康英国男性（284例病例）评估了一个包含19个单核苷酸多态性（SNP）的冠心病基因评分（GS）的性能，该基因评分包括通过全基因组关联研究和候选基因研究确定的变体（使用CARDIoGRAMplusC4D荟萃分析的结果进行加权）。为了改进GS，去除了5个与冠心病关联证据较弱的SNP，并替换为7个强关联SNP，得到一个21-SNP GS。
在调整CRFs后，加权的19-SNP GS与脂质性状相关（p<0.05），并与冠心病相关（每标准差的OR=1.31，p=0.03）。将19-SNP GS添加到QRISK2中显示出鉴别能力提高（受试者操作特征曲线下面积为0.68对0.70，p=0.02），与单独使用QRISK2相比，净重新分类指数为正值（0.07，p=0.04），并且保持了良好的校准（p=0.17）。在调整CRFs后，21-SNP GS也与冠心病相关（每标准差的OR=1.39，1.42×10-3），但与单独使用QRISK2相比，QRISK2加GS的综合评分校准不佳（p=0.03），鉴别能力（p=0.55）或重新分类能力（p=0.10）没有改善。
19-SNP GS与冠心病密切相关，并在英国人群中显示出潜在的临床应用价值。
