Cheng, Yu-Ching, Stanne, Tara M., Giese, Anne-Katrin , Ho, Weang Kee, Traylor, Matthew, Amouyel, Philippe, Holliday, Elizabeth G., Malik, Rainer, Xu, Huichun, Kittner, Steven J., Cole, John W., O'Connell, Jeffrey R., Danesh, John, Rasheed, Asif, Zhao, Wei, Engelter, Stefan, Grond-Ginsbach, Caspar, Kamatani, Yoichiro, Lathrop, Mark, Leys, Didier, Thijs, Vincent, Metso, Tiina M, Tatlisumak, Turgut, Pezzini, Alessandro, Parati, Eugenio A, Norrving, Bo, Bevan, Steve, Rothwell, Peter M., Sudlow, Cathie, Slowik, Agnieszka, Lindgren, Arne, Walters, Matthew R., Jannes, Jim, Shen, Jess, Crosslin, David, Doheny, Kimberly, Laurie, Cathy C., Kanse, Sandip M., Bis, Joshua C., Fornage, Myriam, Mosley, Thomas H., Hopewell, Jemma C., Strauch, Konstantin, Müller-Nurasyid, Martina, Gieger, Christian, Waldenberger, Melanie, Peters, Annette, Meisinger, Christine, Ikram, M Arfan, Longstreth, W. T., Meschia, James F., Seshadri, Sudha, Sharma, Pankaj, Worrall, Bradford, Jern, Christina, Levi, Christopher, Dichgans, Martin, Boncoraglio, Giorgio B., Markus, Hugh S., Debette, Stephanie, Rolfs, Arndt, Saleheen, Danish and Mitchell, Braxton D. (2016) Genome-wide association analysis of young-onset stroke identifies a locus on chromosome 10q25 near HABP2. Stroke: a Journal of Cerebral Circulation, 47 (2). pp. 307-16. ISSN 0039-2499
| Documents |
| ||||
|
PDF
23605 Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke.pdf - Whole Document Available under License Creative Commons Attribution 4.0 International. 286kB |
| Item Type: | Article |
|---|---|
| Item Status: | Live Archive |
Abstract
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 21 968 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.
| Keywords: | Stroke, NotOAChecked |
|---|---|
| Subjects: | C Biological Sciences > C400 Genetics |
| Divisions: | College of Science > School of Life Sciences |
| Related URLs: | |
| ID Code: | 23605 |
| Deposited On: | 01 Aug 2016 20:47 |
Repository Staff Only: item control page