Abstract 053: Genome-wide Tcea3-SNP Interaction Study Identifies Novel QT Interval Loci

Background: QT interval (QT) genome-wide association studies (GWAS) have identified upwards of 35 common variant loci, including SNPs adjacent to putative transcription elongation factor TCEA3. Transcription elongation control has broad effects on gene expression, the misregulation of which is known to influence cardiac conduction system morphogenesis as well as activation or repression of key regulatory genes. Thus, we hypothesized that a genome-wide gene-gene interaction study of TCEA3 lead SNP rs2298632 would identify novel loci that influence QT. Methods: Using 1000 Genomes imputed data (>20 million SNPs) in n=67,445 participants (69% Caucasian; 18% Hispanic/Latino; 11% African American) from 10 studies, we conducted genome-wide meta-analyses to test for the presence of: interaction effect loci by examining rs2298632xSNP interactions on QT; and joint effect loci by simultaneously examining SNP main effects and rs2298632xSNP interactions on QT. Inverse-variance weighted meta-analysis of genomically con...