The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology.
OBJECTIVE
Genome-wide association studies recently identified 2 variants on chromosome 4q25 as susceptibility factors for atrial fibrillation. Interestingly, these variants were subsequently also shown to be associated with stroke. However, it remains unclear whether 4q25 associates with all the stroke subtypes or with cardioembolic stroke in particular, which is often attributable to atrial fibrillation.


METHODS
We performed a large case-control association study in 4199 ischemic stroke patients, all subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6 studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped.


RESULTS
Within cases, the A-allele of rs1906591 was associated with atrial fibrillation (odds ratio, 1.64 [95% CI, 1.43 to 1.90]; P=9.2 . 10(-12)), whereas rs10033464 was only marginally associated. There was an association between overall ischemic stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32]; P=1.2 . 10(-4)). However, this was probably caused by the large effect of stroke of cardioembolic etiology because no relation was obtained in any other subgroup of stroke. The rs10033464 variant failed to show any relationship with ischemic stroke.


CONCLUSIONS
We replicated the association of the rs1906591 variant on chromosome 4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The 4q25 locus failed to associate with noncardiac subtypes of ischemic stroke.
Lemmens
Robin
R
Department of Neurology and Laboratory for Neurobiology, Section of Experimental Neurology, School of Medicine, University of Leuven, Belgium. robin.lemmens@med.kuleuven.be
Buysschaert
Ian
I
Geelen
Veerle
V
Fernandez-Cadenas
Israel
I
Montaner
Joan
J
Schmidt
Helena
H
Schmidt
Reinhold
R
Attia
John
J
Maguire
Jane
J
Levi
Christopher
C
Jood
Katarina
K
Blomstrand
Christian
C
Jern
Christina
C
Wnuk
Marcin
M
Slowik
Agniezska
A
Lambrechts
Diether
D
Thijs
Vincent
V
D000483:Alleles; D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics*; D001315:Australia; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D005060:Europe; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020521:Stroke / Q000150:complications / Q000235:genetics*