Abstract 17262: Identification of a Rare Variant Near Neurexin 1 Associated with Coronary Artery Disease
Background: Genome-wide association studies (GWAS) have identified many common genetic variants that confer modest risk or protection for common diseases. Rarer alleles with minor allele frequencies (MAF) <0.05 often show stronger effects but their signals are typically below commonly accepted GWAS thresholds.
Methods and Results: Here, we tested for associations of less common alleles (0.01<MAF<0.05) with coronary artery disease (CAD) in the Ottawa Heart Genomics Study (OHGS1) that were replicated in two independent GWAS, the Cleveland Clinic/OHGS2 and the Wellcome Trust Case Control Consortium (WTCCC2). Discovery meta-analysis examining 13,017 genotypes identified a novel rare variant associating with CAD near NRXN1 (rs11562945) that attained genome-wide significance for a rare allele (OR=0.51, p=9.64x10−8). Replication meta-analysis of 7 additional GWAS samples with 17,104 individuals confirmed the association between rs11562945 and CAD protection (overall OR=0.63, p=2.84 × 10−7).
Conclusions: Rare alleles of strong effect size can be detected by GWAS. Given NRXN1 is expressed in the vascular system and contributes to angiogenesis, NRXN1 is a plausible candidate in the process of coronary atherosclerosis.
- © 2010 by American Heart Association, Inc.