title: Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.
abstract: OBJECTIVE
  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 × 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Kilarski
authors.forename: Sefanja
authors.initials: S
authors.lastname: Achterberg
authors.forename: William J
authors.initials: WJ
authors.lastname: Devan
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
authors.forename: Rainer
authors.initials: R
authors.lastname: Malik
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
authors.forename: Guillame
authors.initials: G
authors.lastname: Pare
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.forename: Agniesczka
authors.initials: A
authors.lastname: Slowik
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.forename: Matthew
authors.initials: M
authors.lastname: Walters
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: Michele M
authors.initials: MM
authors.lastname: Sale
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Sandling
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: An
authors.initials: A
authors.lastname: Goris
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Cathie
authors.initials: C
authors.lastname: Sudlow
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Bruce
authors.initials: B
authors.lastname: Psaty
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Unnar
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Steven
authors.initials: S
authors.lastname: Kittner
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.forename: Jemma C
authors.initials: JC
authors.lastname: Hopewell
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
authors.forename: James
authors.initials: J
authors.lastname: Meschia
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: Bjorn M
authors.initials: BM
authors.lastname: Hansen
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Kari
authors.initials: K
authors.lastname: Stefanson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
mesh_terms: D002545:Brain Ischemia / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D020521:Stroke / Q000209:etiology / Q000235:genetics*