Abstract 12067: A Genome Wide Association Study (GWAS) of the Early Repolarization Phenotype in BioVU Implicates Variants at 12q22
Introduction: Early repolarization (ER) is a common ECG finding that has previously been reported to be heritable (h2=0.49). When ER is localized to the inferior and/or lateral leads, there has been an association with unexplained sudden cardiac death. We tested the hypothesis that common genetic variation plays a role in its manifestation.
Methods and Results: Cases (N=442) with inferolateral early repolarization, defined as ≥0.1-mV elevation of the J point or ST segment with notching or slurring in at least 2 inferior and/or lateral leads confirmed by physician review, were identified from the BioVU DNA biobank. Cases were genotyped with the Illumina Human Omni1M_Quad platform. Controls (N=2310) were selected from a cohort of individuals with normal ECGs in BioVU as determined by manual review and previously genotyped on the Illumina 660W-Quadv1 platform. A merged set of 332,624 SNPs common to both platforms was created. Logistic regression with the covariates of age and gender was performed separately for individuals self-reported to be Caucasian (260 cases; 1937 controls) and African-American (140; 228). Principle component analysis for the first eigenvector, an indicator of ancestry, was included as a covariate. Two linked SNPs (r2 =0.76) at chr12q22 were associated with ER at genome-wide significance in self-reported Caucasians (P=1.62 x 10-9 and P=6.33 x 10-9, respectively). The first SNP is located in the 3’-UTR of closest gene (found to be expressed in heart), while the second SNP is intergenic. No association was found among the African American subjects.
Conclusion: This GWAS has identified the 12q22 region of self-reported Caucasians to be a possible modulator of malignant early repolarization on the electrocardiogram. The next steps are further replication followed by functional assessment.
- © 2012 by American Heart Association, Inc.