Genetic factors influencing coagulation factor XIII B-subunit contribute to risk of ischemic stroke

Hanscombe, Ken B., Traylor, Matthew, Hysi, Pirro G. , Bevan, Stephen, Dichgans, Martin, Rothwell, Peter M., Worrall, Bradford B., Seshadri, Sudha, Sudlow, Cathie, Williams, Frances M. K., Markus, Hugh S. and Lewis, Cathryn M. (2015) Genetic factors influencing coagulation factor XIII B-subunit contribute to risk of ischemic stroke. Stroke, 46 (8). pp. 2069-2074. ISSN 0039-2499

Full content URL:

Full text not available from this repository.

Item Type:Article
Item Status:Live Archive


Background and Purpose—Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes.

Methods—Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls—the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke.

Results—One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10−04); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10−04) and the cardioembolic subtype (smallest P=1.7×10−04). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=−0.71, P=0.01) and the cardioembolic subtype (rG=−0.80, P=0.03).

Conclusions—Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype.

Keywords:Genome-wide association study, Coagulation, Stroke, JCOpen
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
ID Code:19449
Deposited On:06 Nov 2015 11:10

Repository Staff Only: item control page