Journal article

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 MM Howson, Michael Inouye, Martin Dichgans

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

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, ..

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Grants

Awarded by Australian Heart Foundation Career Development Fellowship


Awarded by NHMRC Early Career Fellowship


Awarded by European Union's Horizon 2020 research and innovation programme


Awarded by DFG as part of the Munich Cluster for Systems Neurology


Awarded by DFG


Awarded by UK Medical Research Council


Awarded by British Heart Foundation



Funding Acknowledgements

This study was supported in part by the Victorian Government's OIS Program. M.I. was supported by an NHMRC and Australian Heart Foundation Career Development Fellowship (no. 1061435). G.A. was supported by an NHMRC Early Career Fellowship (no. 1090462). M.D. acknowledges funding from the European Union's Horizon 2020 research and innovation programme (grant agreements no. 666881, SVDs@target and no. 667375, CoSTREAM); and the DFG as part of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy), the CRC 1123 (B3), and DI 722/13-1n. J.D. is funded by the National Institute for Health Research (Senior Investigator Award). M.I. and J.M.M.H. are funded by the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). This work was supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html. Data on coronary artery disease/myocardial infarction have been contributed by CARDIoGRAMplusC4D investigators and have been downloaded from www.cardiogramplusc4d.org. UK Biobank analyses were conducted under project 26865.