Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
Nature Publishing Group UK
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Abraham, G., Malik, R., Yonova-Doing, E., Salim, A., Wang, T., Danesh, J., Butterworth, A. S., et al. (2019). Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke. Nature Communications, 10 (1)https://doi.org/10.1038/s41467-019-13848-1
Funder: Munich Cluster for Systems Neurology (EXC 1010 SyNergy) and the CRC 1123 (B3).
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.
Article, /631/208/205/2138, /631/208/212/2166, /692/617/375/534, /692/499, /38/43, article
Department of Health and Human Services, State Government of Victoria (Department of Health and Human Services) (Operational Infrastructure Support Program)
Department of Health | National Health and Medical Research Council (NHMRC) (CDF 1061435, ECF 1090462)
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (666881, 667375)
DH | National Institute for Health Research (NIHR) (Senior Investigator Award)
RCUK | Medical Research Council (MRC) (MR/L003120/1)
British Heart Foundation (BHF) (RG/13/13/30194)
External DOI: https://doi.org/10.1038/s41467-019-13848-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/315458