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

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Abraham, Gad 
Malik, Rainer 
Yonova-Doing, Ekaterina 
Salim, Agus 
Wang, Tingting 

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.

Aged, Blood Pressure, Body Mass Index, Brain Ischemia, Comorbidity, Datasets as Topic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Male, Medical History Taking, Middle Aged, Polymorphism, Single Nucleotide, Predictive Value of Tests, Risk Assessment, Smoking, United Kingdom
Journal Title
Nat Commun
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Springer Science and Business Media LLC
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
European Commission Horizon 2020 (H2020) Societal Challenges (667375)
British Heart Foundation (RG/18/13/33946)