Abstract TP163: Exome Array Analysis of Ischemic Stroke in a South Swedish Population
Background: Genome-wide association (GWA) studies have identified a few risk loci for ischemic stroke. Yet, these variants can explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis of rare coding variants for ischemic stroke.
Methods: Patients with ischemic stroke (n=2,385) and control subjects (n=6,077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis was performed of non-synonymous variants with minor allele frequency <5% (n=33,130). A separate genome-wide association (GWA) analysis was also performed, based on 700,000 genotyped common markers and subsequent imputation according to 1000 Genomes.
Results: No variant in the exome analysis was significantly associated with ischemic stroke after Bonferroni correction (all p>1.5x10-6). The two strongest associations were found for missense variants in the genes DNAH11 (odds ratio: 0.14 [95% confidence interval: 0.05-0.41], p=2.9x10-4), and ATF6 (odds ratio: 2.03 [1.38-2.98], p=3.6x10-4). The GWA analysis showed that the sample was homogenous (median genomic inflation factor=1.006). No genome-wide significant association with overall ischemic stroke risk was found (all p>5x10-8). However, previously reported associations for the PITX2 and ZFHX3 gene loci with the subtype cardioembolic stroke were replicated (p=7x10-15 and 6x10-3).
Conclusion: None of the coding non-synonymous genetic variants reached the pre-defined significance level in this exome array analysis for ischemic stroke. Further studies on exome variation should be performed in even larger samples to identify novel genetic risk factors.
Author Disclosures: M. Söderholm: None. P. Almgren: None. K. Jood: None. T. Stanne: None. M. Olsson: None. A. Illinca: None. G. Andsberg: None. B. Norrving: None. G. Engström: None. O. Melander: None. C. Jern: None. A. Lindgren: None.
- © 2016 by American Heart Association, Inc.