Abstract
Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors’, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
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Acknowledgements
The authors acknowledge the Knut and Alice Wallenberg Foundation for its economic support of the SWEGENE DNA-extraction facility. DNA extraction and preparation for LSR was performed by Biobank Skåne, Labmedicin Skåne. This study was supported by grants from the European Research Council (StG-282255), the Swedish Research Council (K2011-65X-14605-09-6 and K2010-61X-20378-04-3), the Swedish state (ALFGBG-148861), the Swedish Heart and Lung Foundation, the Swedish Stroke Association, the Medical Faculty of Lund University, Malmö University Hospital, the Freemasons Lodge of Instruction EOS in Lund, the Region Skane, the Lennart Hansson Memorial Fund, the Rune and Ulla Amlöv, John and Brit Wennerström, Lars Hierta, Edit Jacobson, Tore Nilsson, Albert Påhlsson, Crafoord, Ernhold Lundströms, Hulda and Conrad Mossfelt, and the King Gustaf V and Queen Victoria research foundations.
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Fava, C., Sjögren, M., Olsson, S. et al. A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case–control study. Eur J Hum Genet 23, 969–974 (2015). https://doi.org/10.1038/ejhg.2014.212
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DOI: https://doi.org/10.1038/ejhg.2014.212
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