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

Gad Abraham (), Rainer Malik, Ekaterina Yonova-Doing, Agus Salim, Tingting Wang, John Danesh, Adam S. Butterworth, Joanna M. M. Howson, Michael Inouye () and Martin Dichgans ()
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Gad Abraham: Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute
Rainer Malik: University Hospital, Ludwig-Maximilians-Universität LMU
Ekaterina Yonova-Doing: University of Cambridge
Agus Salim: Baker Heart and Diabetes Institute
Tingting Wang: Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute
John Danesh: University of Cambridge
Adam S. Butterworth: University of Cambridge
Joanna M. M. Howson: University of Cambridge
Michael Inouye: Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute
Martin Dichgans: University Hospital, Ludwig-Maximilians-Universität LMU

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13848-1

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