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

Laura L. Kilarski, Sefanja Achterberg, William J. Devan, Matthew Traylor, Rainer Malik, Arne Lindgren, Guillame Pare, Pankaj Sharma, Agniesczka Slowik, Vincent Thijs, Matthew Walters, Bradford B. Worrall, Michele M. Sale, Ale Algra, L. Jaap Kappelle, Cisca Wijmenga, Bo Norrving, Johanna K. Sandling, Lars Rönnblom, An Goris & 28 others Andre Franke, Cathie Sudlow, Peter M. Rothwell, Christopher Levi, Elizabeth G. Holliday, Myriam Fornage, Bruce Psaty, Solveig Gretarsdottir, Unnar Thorsteinsdottir, Sudha Seshadri, Braxton D. Mitchell, Steven Kittner, Robert Clarke, Jemma C. Hopewell, Joshua C. Bis, Giorgio B. Boncoraglio, James Meschia, M. Arfan Ikram, Bjorn M. Hansen, Joan Montaner, Gudmar Thorleifsson, Kari Stefanson, Jonathan Rosand, Paul I.W. De Bakker, Martin Farrall, Martin Dichgans, Hugh S. Markus, Steve Bevan

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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 5 7.12 3 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 5 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.

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.

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.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalNeurology
Volume83
Issue number8
DOIs
StatePublished - Aug 19 2014
Externally publishedYes

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Meta-Analysis
Stroke
Cerebral Hemorrhage
Genome-Wide Association Study
Odds Ratio
Genetic Loci
Computer Simulation
Single Nucleotide Polymorphism
Chromosomes

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kilarski, L. L., Achterberg, S., Devan, W. J., Traylor, M., Malik, R., Lindgren, A., ... Bevan, S. (2014). Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12. Neurology, 83(8), 678-685. https://doi.org/10.1212/WNL.0000000000000707

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; Pare, Guillame; Sharma, Pankaj; Slowik, Agniesczka; Thijs, Vincent; Walters, Matthew; Worrall, Bradford B.; Sale, Michele M.; Algra, Ale; Kappelle, L. Jaap; Wijmenga, Cisca; Norrving, Bo; Sandling, Johanna K.; Rönnblom, Lars; Goris, An; Franke, Andre; Sudlow, Cathie; Rothwell, Peter M.; Levi, Christopher; Holliday, Elizabeth G.; Fornage, Myriam; Psaty, Bruce; Gretarsdottir, Solveig; Thorsteinsdottir, Unnar; Seshadri, Sudha; Mitchell, Braxton D.; Kittner, Steven; Clarke, Robert; Hopewell, Jemma C.; Bis, Joshua C.; Boncoraglio, Giorgio B.; Meschia, James; Ikram, M. Arfan; Hansen, Bjorn M.; Montaner, Joan; Thorleifsson, Gudmar; Stefanson, Kari; Rosand, Jonathan; De Bakker, Paul I.W.; Farrall, Martin; Dichgans, Martin; Markus, Hugh S.; Bevan, Steve.

In: Neurology, Vol. 83, No. 8, 19.08.2014, p. 678-685.

Research output: Contribution to journalArticle

Kilarski, LL, Achterberg, S, Devan, WJ, Traylor, M, Malik, R, Lindgren, A, Pare, G, Sharma, P, Slowik, A, Thijs, V, Walters, M, Worrall, BB, Sale, MM, Algra, A, Kappelle, LJ, Wijmenga, C, Norrving, B, Sandling, JK, Rönnblom, L, Goris, A, Franke, A, Sudlow, C, Rothwell, PM, Levi, C, Holliday, EG, Fornage, M, Psaty, B, Gretarsdottir, S, Thorsteinsdottir, U, Seshadri, S, Mitchell, BD, Kittner, S, Clarke, R, Hopewell, JC, Bis, JC, Boncoraglio, GB, Meschia, J, Ikram, MA, Hansen, BM, Montaner, J, Thorleifsson, G, Stefanson, K, Rosand, J, De Bakker, PIW, Farrall, M, Dichgans, M, Markus, HS & Bevan, S 2014, 'Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12', Neurology, vol. 83, no. 8, pp. 678-685. https://doi.org/10.1212/WNL.0000000000000707
Kilarski LL, Achterberg S, Devan WJ, Traylor M, Malik R, Lindgren A et al. Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12. Neurology. 2014 Aug 19;83(8):678-685. https://doi.org/10.1212/WNL.0000000000000707
Kilarski, Laura L. ; Achterberg, Sefanja ; Devan, William J. ; Traylor, Matthew ; Malik, Rainer ; Lindgren, Arne ; Pare, Guillame ; Sharma, Pankaj ; Slowik, Agniesczka ; Thijs, Vincent ; Walters, Matthew ; Worrall, Bradford B. ; Sale, Michele M. ; Algra, Ale ; Kappelle, L. Jaap ; Wijmenga, Cisca ; Norrving, Bo ; Sandling, Johanna K. ; Rönnblom, Lars ; Goris, An ; Franke, Andre ; Sudlow, Cathie ; Rothwell, Peter M. ; Levi, Christopher ; Holliday, Elizabeth G. ; Fornage, Myriam ; Psaty, Bruce ; Gretarsdottir, Solveig ; Thorsteinsdottir, Unnar ; Seshadri, Sudha ; Mitchell, Braxton D. ; Kittner, Steven ; Clarke, Robert ; Hopewell, Jemma C. ; Bis, Joshua C. ; Boncoraglio, Giorgio B. ; Meschia, James ; Ikram, M. Arfan ; Hansen, Bjorn M. ; Montaner, Joan ; Thorleifsson, Gudmar ; Stefanson, Kari ; Rosand, Jonathan ; De Bakker, Paul I.W. ; Farrall, Martin ; Dichgans, Martin ; Markus, Hugh S. ; Bevan, Steve. / Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12. In: Neurology. 2014 ; Vol. 83, No. 8. pp. 678-685.
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abstract = "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 5 7.12 3 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 5 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.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.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.",
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T1 - Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12

AU - Kilarski, Laura L.

AU - Achterberg, Sefanja

AU - Devan, William J.

AU - Traylor, Matthew

AU - Malik, Rainer

AU - Lindgren, Arne

AU - Pare, Guillame

AU - Sharma, Pankaj

AU - Slowik, Agniesczka

AU - Thijs, Vincent

AU - Walters, Matthew

AU - Worrall, Bradford B.

AU - Sale, Michele M.

AU - Algra, Ale

AU - Kappelle, L. Jaap

AU - Wijmenga, Cisca

AU - Norrving, Bo

AU - Sandling, Johanna K.

AU - Rönnblom, Lars

AU - Goris, An

AU - Franke, Andre

AU - Sudlow, Cathie

AU - Rothwell, Peter M.

AU - Levi, Christopher

AU - Holliday, Elizabeth G.

AU - Fornage, Myriam

AU - Psaty, Bruce

AU - Gretarsdottir, Solveig

AU - Thorsteinsdottir, Unnar

AU - Seshadri, Sudha

AU - Mitchell, Braxton D.

AU - Kittner, Steven

AU - Clarke, Robert

AU - Hopewell, Jemma C.

AU - Bis, Joshua C.

AU - Boncoraglio, Giorgio B.

AU - Meschia, James

AU - Ikram, M. Arfan

AU - Hansen, Bjorn M.

AU - Montaner, Joan

AU - Thorleifsson, Gudmar

AU - Stefanson, Kari

AU - Rosand, Jonathan

AU - De Bakker, Paul I.W.

AU - Farrall, Martin

AU - Dichgans, Martin

AU - Markus, Hugh S.

AU - Bevan, Steve

PY - 2014/8/19

Y1 - 2014/8/19

N2 - 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 5 7.12 3 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 5 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.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.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.

AB - 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 5 7.12 3 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 5 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.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.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.

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