- Title
- Genome-wide association analysis of young-onset stroke identifies a locus on chromosome 10q25 near HABP2
- Creator
- Cheng, Yu-Ching; Stanne, Tara M.; Cole, John W.; O'Connell, Jeffrey R.; Danesh, John; Rasheed, Asif; Zhao, Wei; Engelter, Stefan; Grond-Ginsbach, Caspar; Kamatani, Yoichiro; Lathrop, Mark; Leys, Didier; Giese, Anne-Katrin; Levi, Christopher; Ho, Weang Kee; Traylor, Matthew; Amouyel, Philippe; Holliday, Elizabeth G.; Malik, Rainer; Xu, Huichun; Kittner, Steven J.
- Relation
- Stroke Vol. 47, Issue 2, p. 307-316
- Publisher Link
- http://dx.doi.org/10.1161/STROKEAHA.115.011328
- Publisher
- Lippincott Williams & Wilkins
- Resource Type
- journal article
- Date
- 2016
- Description
- 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<5x10-6 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=9.5x10-9). 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.
- Subject
- factor VII; genetics; genome-wide analysis; ischemic stroke; stroke
- Identifier
- http://hdl.handle.net/1959.13/1321533
- Identifier
- uon:24389
- Identifier
- ISSN:0039-2499
- Language
- eng
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