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

ISGC, WTCCC2, Bellenguez, Céline, Bevan, Steve, Gschwendtner, Andreas, Spencer, Chris C. A., Burgess, Annette I., Pirinen, Matti, Jackson, Caroline A., Traylor, Matthew, Strange, Amy, Su, Zhan, Band, Gavin, Syme, Paul D., Malik, Rainer, Pera, Joanna, Norrving, Bo, Lemmens, Robin, Freeman, Colin, Schanz, Renata, James, Tom, Poole, Deborah, Murphy, Lee, Segal, Helen, Cortellini, Lynelle, Cheng, Yu-Ching, Woo, Daniel, Nalls, Michael A., Muller-Myhsok, Bertram, Meisinger, Christa, Seedorf, Udo, Ross-Adams, Helen, Boonen, Steven, Wloch-Kopec, Dorota, Valant, Valerie, Slark, Julia, Furie, Karen, Delavaran, Hossein, Langford, Cordelia, Deloukas, Panos, Edkins, Sarah, Hunt, Sarah, Gray, Emma, Dronov, Serge, Peltonen, Leena, Gretarsdottir, Solveig, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Stefansson, Kari, Boncoraglio, Giorgio B., Parati, Eugenio A., Attia, John, Holliday, Elizabeth, Levi, Chris, Franzosi, Maria-Grazia, Goel, Anuj, Helgadottir, Anna, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz, Mathew, Christopher G., Palmer, Colin N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Worrall, Bradford B., Kittner, Steven J., Kissela, Brett, Mitchell, Braxton D., Meschia, James F., Thijs, Vincent, Lindgren, Arne, Macleod, Mary Joan, Slowik, Agnieszka, Walters, Matthew, Rosand, Jonathan, Sharma, Pankaj, Farrall, Martin, Sudlow, Cathie L. M., Rothwell, Peter M., Dichgans, Martin, Donnelly, Peter and Markus, Hugh S. (2012) Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nature Genetics, 44 3: 328-333. doi:10.1038/ng.1081


Author ISGC
WTCCC2
Bellenguez, Céline
Bevan, Steve
Gschwendtner, Andreas
Spencer, Chris C. A.
Burgess, Annette I.
Pirinen, Matti
Jackson, Caroline A.
Traylor, Matthew
Strange, Amy
Su, Zhan
Band, Gavin
Syme, Paul D.
Malik, Rainer
Pera, Joanna
Norrving, Bo
Lemmens, Robin
Freeman, Colin
Schanz, Renata
James, Tom
Poole, Deborah
Murphy, Lee
Segal, Helen
Cortellini, Lynelle
Cheng, Yu-Ching
Woo, Daniel
Nalls, Michael A.
Muller-Myhsok, Bertram
Meisinger, Christa
Seedorf, Udo
Ross-Adams, Helen
Boonen, Steven
Wloch-Kopec, Dorota
Valant, Valerie
Slark, Julia
Furie, Karen
Delavaran, Hossein
Langford, Cordelia
Deloukas, Panos
Edkins, Sarah
Hunt, Sarah
Gray, Emma
Dronov, Serge
Peltonen, Leena
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Stefansson, Kari
Boncoraglio, Giorgio B.
Parati, Eugenio A.
Attia, John
Holliday, Elizabeth
Levi, Chris
Franzosi, Maria-Grazia
Goel, Anuj
Helgadottir, Anna
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Jankowski, Janusz
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Worrall, Bradford B.
Kittner, Steven J.
Kissela, Brett
Mitchell, Braxton D.
Meschia, James F.
Thijs, Vincent
Lindgren, Arne
Macleod, Mary Joan
Slowik, Agnieszka
Walters, Matthew
Rosand, Jonathan
Sharma, Pankaj
Farrall, Martin
Sudlow, Cathie L. M.
Rothwell, Peter M.
Dichgans, Martin
Donnelly, Peter
Markus, Hugh S.
Title Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Formatted title
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2012-03-01
Sub-type Article (original research)
DOI 10.1038/ng.1081
Open Access Status Not yet assessed
Volume 44
Issue 3
Start page 328
End page 333
Total pages 6
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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 × 10 ; 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.
Formatted 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 × 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.
Keyword Atrial fibrillation
Histone deacetylases
Susceptibility loci
Algorithm
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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