title: Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?
abstract: OBJECTIVE
  The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes.
  
  
  METHODS
  We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately.
  
  
  RESULTS
  SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect.
  
  
  CONCLUSIONS
  Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.
authors: Department of Clinical Sciences, Lund University, Lund, Sweden. hakan.lovkvist@skane.se
authors: H
authors: H
authors: Lövkvist
authors: M
authors: M
authors: Sjögren
authors: P
authors: P
authors: Höglund
authors: G
authors: G
authors: Engström
authors: C
authors: C
authors: Jern
authors: S
authors: S
authors: Olsson
authors: J G
authors: JG
authors: Smith
authors: B
authors: B
authors: Hedblad
authors: G
authors: G
authors: Andsberg
authors: H
authors: H
authors: Delavaran
authors: K
authors: K
authors: Jood
authors: U
authors: U
authors: Kristoffersson
authors: B
authors: B
authors: Norrving
authors: O
authors: O
authors: Melander
authors: A
authors: A
authors: Lindgren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*; D055815:Young Adult
keywords: CARDIoGRAM; coronary artery disease; genetic risk score; genome-wide association study; ischaemic stroke; single-nucleotide polymorphism