@article {6598, title = {Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval.}, journal = {Epidemiology}, volume = {25}, year = {2014}, month = {2014 Nov}, pages = {790-8}, abstract = {

BACKGROUND: QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations.

METHODS: Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16,398), African (n = 5,437), American Indian (n = 5,032), Hispanic (n = 1,143), and Asian (n = 932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran{\textquoteright}s Q test.

RESULTS: Of 21 SNPs, 7 showed consistent direction of effect across all 5 populations, and an additional 9 had estimated effects that were consistent across 4 populations. Despite consistent direction of effect, 9 of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity.

CONCLUSIONS: These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT.

}, keywords = {Aged, Continental Population Groups, Electrocardiography, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Long QT Syndrome, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Risk Factors}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000000168}, author = {Seyerle, Amanda A and Young, Alicia M and Jeff, Janina M and Melton, Phillip E and Jorgensen, Neal W and Lin, Yi and Carty, Cara L and Deelman, Ewa and Heckbert, Susan R and Hindorff, Lucia A and Jackson, Rebecca D and Martin, Lisa W and Okin, Peter M and Perez, Marco V and Psaty, Bruce M and Soliman, Elsayed Z and Whitsel, Eric A and North, Kari E and Laston, Sandra and Kooperberg, Charles and Avery, Christy L} }