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

Autoria(s): Bellenguez, C.; Bevan, S.; Gschwendtner, A.; Spencer, C. C. A.; Burgess, A. I.; Pirinen, M.; Jackson, C. A.; Traylor, M.; Strange, A.; Su, Z.; Band, G.; Syme, P. D.; Malik, R.; Pera, J.; Bo, N.; Lemmens, R.; Freeman, C.; Schanz, R.; James, T.; Poole, D.; Murphy, L.; Segal, H.; Cortellini, L.; Cheng, Y. C.; Woo, D.; Nalls, M. A.; Müller-Myhsok, B.; Meisinger, C.; Seedorf, U.; Ross-Adams, H.; Boonen, S.; Wloch-Kopec, D.; Valant, V.; Slark, J.; Furie, K.; Delavaran, H.; Langford, C.; Deloukas, P.; Edkins, S.; Hunt, S.; Gray, E.; Dronov, S.; Peltonen, L.; Gretarsdottir, S.; Thorleifsson, G.; Thorsteinsdottir, U.; Stefansson, K.; Boncoraglio, G. B.; Parati, E. A.; Attia, J.; Holliday, E.; Levi, C.; Franzosi, M. G.; Goel, A.; Helgadottir, A.; Blackwell, J. M.; Bramon, E.; Brown, M. A.; Casas, J. P.; Corvin, A.; Duncanson, A.; Jankowski, J.; Mathew, C. G.; Palmer, C. N. A.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Trembath, R. C.; Viswanathan, A. C.; Wood, N. W.; Worrall, B. B.; Kittner, S. J.; Mitchell, B. D.; Kissela, B.; Meschia, J. F.; Thijs, V.; Lindgren, A.; MacLeod, M. J.; Slowik, A.; Walters, M.; Rosand, J.; Sharma, P.; Farrall, M.; Sudlow, C. L. M.; Rothwell, P. M.; Dichgans, M.; Donnelly, P.; Markus, H. S.
Data(s)

2012
Resumo

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.
Identificador

http://eprints.qut.edu.au/87605/
Publicador

Nature Publishing Group
Relação

DOI:10.1038/ng.1081

Bellenguez, C., Bevan, S., Gschwendtner, A., Spencer, C. C. A., Burgess, A. I., Pirinen, M., Jackson, C. A., Traylor, M., Strange, A., Su, Z., Band, G., Syme, P. D., Malik, R., Pera, J., Bo, N., Lemmens, R., Freeman, C., Schanz, R., James, T., Poole, D., Murphy, L., Segal, H., Cortellini, L., Cheng, Y. C., Woo, D., Nalls, M. A., Müller-Myhsok, B., Meisinger, C., Seedorf, U., Ross-Adams, H., Boonen, S., Wloch-Kopec, D., Valant, V., Slark, J., Furie, K., Delavaran, H., Langford, C., Deloukas, P., Edkins, S., Hunt, S., Gray, E., Dronov, S., Peltonen, L., Gretarsdottir, S., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Boncoraglio, G. B., Parati, E. A., Attia, J., Holliday, E., Levi, C., Franzosi, M. G., Goel, A., Helgadottir, A., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Jankowski, J., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Worrall, B. B., Kittner, S. J., Mitchell, B. D., Kissela, B., Meschia, J. F., Thijs, V., Lindgren, A., MacLeod, M. J., Slowik, A., Walters, M., Rosand, J., Sharma, P., Farrall, M., Sudlow, C. L. M., Rothwell, P. M., Dichgans, M., Donnelly, P., & Markus, H. S. (2012) Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nature Genetics, 44(3), pp. 328-333.
Direitos

© 2012 Nature America, Inc.
Fonte

School of Biomedical Sciences; Institute of Health and Biomedical Innovation
Palavras-Chave #article #brain ischemia #Caucasian #chromosome 7p #confidence interval #controlled study #female #gene #gene locus #gene replication #genetic association #genetic code #genetic heterogeneity #genetic variability #great blood vessel #histone deacetylase 9 gene #human #major clinical study #male #priority journal #risk #Chromosomes #Human #Pair 7 #European Continental Ancestry Group #Genetic Predisposition to Disease #Genome-Wide Association Study #Genotype #Histone Deacetylases #Humans #Odds Ratio #Polymorphism #Single Nucleotide #Repressor Proteins #Stroke
Tipo

Journal Article
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