2016-02-01
Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2
Publication
Publication
Stroke , Volume 47 - Issue 2 p. 307- 316
Background and Purpose - Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early-versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset < 60 years. Methods. The discovery stage of our genome-wide association studies included 4505 cases and 21968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10-6 and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. Results.One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10-9). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII.activating protease levels, a product of HABP2. Conclusions.HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.
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| doi.org/10.1161/STROKEAHA.115.011328, hdl.handle.net/1765/90124 | |
| Stroke | |
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| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Cheng, Y.-C., Stanne, T. M., Giese, A.-K., Ho, W. K., Traylor, M., Amouyel, P., … Mitchell, B. (2016). Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2. Stroke, 47(2), 307–316. doi:10.1161/STROKEAHA.115.011328 |
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