Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke

Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
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基因组风险评分提供的预测性能可与缺血性中风的临床危险因素相媲美

DOI:
10.1101/689935
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Abraham G
Abraham G
中科院分区:
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文献类型:
--
作者:
Abraham G

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最近的中风全基因组关联研究已经能够生成基因组风险评分(GRS),但与已建立的中风风险因素相比,其预测能力一直很低。在这里,我们使用元评分方法,开发了缺血性卒中(IS)的元GRS,并在英国生物样本库中分析了该评分(n= 395,393; 3075例75岁以下的IS事件)。IS的MetaGRS风险比(1.26,95% CI 1.22-1.31/MetaGRS标准差)是先前GRS的两倍,确定了单基因风险水平的个体子集:前0.25%的MetaGRS具有三倍的IS风险。与几个风险因素(如家族史、血压、体重指数和吸烟)相比,MetaGRS具有相似或更高的预测性。我们估计了具有不同基因组风险水平的个体所需的可改变风险因素的减少,并建议,对于具有高MetaGRS的个体,达到当前指南推荐的风险因素水平可能不足以减轻风险。
Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n= 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22–1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.
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