Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Nat Commun. 2019 Dec 20;10(1):5819. doi: 10.1038/s41467-019-13848-1.
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.
最近的中风全基因组关联研究使得能够生成基因组风险评分（GRS），但与已确立的中风风险因素相比，其预测能力相当有限。在这里，我们使用荟萃评分方法，为缺血性中风（IS）开发了一个荟萃 GRS，并在英国生物库中对该评分进行了分析（n=395393；75 岁时 3075 例 IS 事件）。荟萃 GRS 与 IS 的风险比为 1.26（每荟萃 GRS 标准差增加 1.22-1.31），是之前 GRS 的两倍，确定了处于单基因风险水平的个体亚组：荟萃 GRS 最高的 0.25%人群发生 IS 的风险增加三倍。与其他风险因素（如家族史、血压、体重指数和吸烟）相比，荟萃 GRS 的预测能力相似或更高。我们估计了不同基因组风险水平个体需要降低的可改变风险因素，并建议对于具有高荟萃 GRS 的个体，达到当前指南推荐的风险因素水平可能不足以降低风险。
