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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Laura L. Kilarski
  • Sefanja Achterberg
  • William J. Devan
  • Matthew Traylor
  • Rainer Malik
  • Guillame Pare
  • Pankaj Sharma
  • Agniesczka Slowik
  • Vincent Thijs
  • Matthew Walters
  • Bradford B. Worrall
  • Michele M. Sale
  • Ale Algra
  • L. Jaap Kappelle
  • Cisca Wijmenga
  • Johanna K. Sandling
  • Lars Roennblom
  • An Goris
  • 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
  • Joan Montaner
  • Gudmar Thorleifsson
  • Kari Stefanson
  • Jonathan Rosand
  • Paul I. W. de Bakker
  • Martin Farrall
  • Martin Dichgans
  • Hugh S. Markus
  • Steve Bevan
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Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Pages (from-to)678-685
JournalNeurology
Volume83
Issue number8
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes