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Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12

Kilarski, Laura L.; Achterberg, Sefanja; Devan, William J.; Traylor, Matthew; Malik, Rainer; Lindgren, Arne LU ; Pare, Guillame; Sharma, Pankaj; Slowik, Agniesczka and Thijs, Vincent, et al. (2014) In Neurology 83(8). p.678-685
Abstract
Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases... (More)
Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 x 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage. (Less)
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Contribution to journal
publication status
published
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Neurology
volume
83
issue
8
pages
678 - 685
publisher
American Academy of Neurology
external identifiers
  • wos:000340727800007
  • scopus:84920146738
ISSN
1526-632X
DOI
10.1212/WNL.0000000000000707
language
English
LU publication?
yes
id
c4a18e4a-5ded-4d3b-90f6-509ed621a7b1 (old id 4648982)
alternative location
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150131/
date added to LUP
2014-10-01 07:26:53
date last changed
2017-10-01 04:00:51
@article{c4a18e4a-5ded-4d3b-90f6-509ed621a7b1,
  abstract     = {Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 x 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.},
  author       = {Kilarski, Laura L. and Achterberg, Sefanja and Devan, William J. and Traylor, Matthew and Malik, Rainer and Lindgren, Arne and Pare, Guillame and Sharma, Pankaj and Slowik, Agniesczka and Thijs, Vincent and Walters, Matthew and Worrall, Bradford B. and Sale, Michele M. and Algra, Ale and Kappelle, L. Jaap and Wijmenga, Cisca and Norrving, Bo and Sandling, Johanna K. and Roennblom, Lars and Goris, An and Franke, Andre and Sudlow, Cathie and Rothwell, Peter M. and Levi, Christopher and Holliday, Elizabeth G. and Fornage, Myriam and Psaty, Bruce and Gretarsdottir, Solveig and Thorsteinsdottir, Unnar and Seshadri, Sudha and Mitchell, Braxton D. and Kittner, Steven and Clarke, Robert and Hopewell, Jemma C. and Bis, Joshua C. and Boncoraglio, Giorgio B. and Meschia, James and Ikram, M. Arfan and Hansen, Björn and Montaner, Joan and Thorleifsson, Gudmar and Stefanson, Kari and Rosand, Jonathan and de Bakker, Paul I. W. and Farrall, Martin and Dichgans, Martin and Markus, Hugh S. and Bevan, Steve},
  issn         = {1526-632X},
  language     = {eng},
  number       = {8},
  pages        = {678--685},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000000707},
  volume       = {83},
  year         = {2014},
}