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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Bellenguez, Celine; Bevan, Steve; Gschwendtner, Andreas; Spencer, Chris C. A.; Burgess, Annette I.; Pirinen, Matti; Jackson, Caroline A.; Traylor, Matthew; Strange, Amy and Su, Zhan, et al. (2012) In Nature Genetics 44(3). p.141-328
Abstract
Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x... (More)
Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes. (Less)
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Nature Genetics
volume
44
issue
3
pages
141 - 328
publisher
Nature Publishing Group
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  • wos:000300843600021
  • scopus:84863393715
ISSN
1546-1718
DOI
10.1038/ng.1081
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English
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9f4ca94e-282a-49a3-98de-890883b7ea45 (old id 2379201)
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2012-04-02 09:22:04
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@article{9f4ca94e-282a-49a3-98de-890883b7ea45,
  abstract     = {Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.},
  author       = {Bellenguez, Celine and Bevan, Steve and Gschwendtner, Andreas and Spencer, Chris C. A. and Burgess, Annette I. and Pirinen, Matti and Jackson, Caroline A. and Traylor, Matthew and Strange, Amy and Su, Zhan and Band, Gavin and Syme, Paul D. and Malik, Rainer and Pera, Joanna and Norrving, Bo and Lemmens, Robin and Freeman, Colin and Schanz, Renata and James, Tom and Poole, Deborah and Murphy, Lee and Segal, Helen and Cortellini, Lynelle and Cheng, Yu-Ching and Woo, Daniel and Nalls, Michael A. and Mueller-Myhsok, Bertram and Meisinger, Christa and Seedorf, Udo and Ross-Adams, Helen and Boonen, Steven and Wloch-Kopec, Dorota and Valant, Valerie and Slark, Julia and Furie, Karen and Delavaran, Hossein and Langford, Cordelia and Deloukas, Panos and Edkins, Sarah and Hunt, Sarah and Gray, Emma and Dronov, Serge and Peltonen, Leena and Gretarsdottir, Solveig and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Stefansson, Kari and Boncoraglio, Giorgio B. and Parati, Eugenio A. and Attia, John and Holliday, Elizabeth and Levi, Chris and Franzosi, Maria-Grazia and Goel, Anuj and Helgadottir, Anna and Blackwell, Jenefer M. and Bramon, Elvira and Brown, Matthew A. and Casas, Juan P. and Corvin, Aiden and Duncanson, Audrey and Jankowski, Janusz and Mathew, Christopher G. and Palmer, Colin N. A. and Plomin, Robert and Rautanen, Anna and Sawcer, Stephen J. and Trembath, Richard C. and Viswanathan, Ananth C. and Wood, Nicholas W. and Worrall, Bradford B. and Kittner, Steven J. and Mitchell, Braxton D. and Kissela, Brett and Meschia, James F. and Thijs, Vincent and Lindgren, Arne and Macleod, Mary Joan and Slowik, Agnieszka and Walters, Matthew and Rosand, Jonathan and Sharma, Pankaj and Farrall, Martin and Sudlow, Cathie L. M. and Rothwell, Peter M. and Dichgans, Martin and Donnelly, Peter and Markus, Hugh S.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {3},
  pages        = {141--328},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke},
  url          = {http://dx.doi.org/10.1038/ng.1081},
  volume       = {44},
  year         = {2012},
}