%0 Journal Article %J Epidemiology %D 2014 %T Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval. %A Seyerle, Amanda A %A Young, Alicia M %A Jeff, Janina M %A Melton, Phillip E %A Jorgensen, Neal W %A Lin, Yi %A Carty, Cara L %A Deelman, Ewa %A Heckbert, Susan R %A Hindorff, Lucia A %A Jackson, Rebecca D %A Martin, Lisa W %A Okin, Peter M %A Perez, Marco V %A Psaty, Bruce M %A Soliman, Elsayed Z %A Whitsel, Eric A %A North, Kari E %A Laston, Sandra %A Kooperberg, Charles %A Avery, Christy L %K Aged %K Continental Population Groups %K Electrocardiography %K Female %K Genetic Predisposition to Disease %K Haplotypes %K Humans %K Long QT Syndrome %K Male %K Middle Aged %K Phenotype %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Quantitative Trait, Heritable %K Risk Factors %X

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'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.

%B Epidemiology %V 25 %P 790-8 %8 2014 Nov %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/25166880?dopt=Abstract %R 10.1097/EDE.0000000000000168