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Seyerle, Amanda A.; Young, Alicia M.; Jeff, Janina M.; Melton, Phillip E.; Jorgensen, Neal W.; Lin, Yi; Carty, Cara L.; Deelman, Ewa; Heckbert, Susan R.; Hindorff, Lucia A.; Jackson, Rebecca D.; Martin, Lisa W.; Okin, Peter M.; Perez, Marco V.; Psaty, Bruce M.; Soliman, Elsayed Z.; Whitsel, Eric A.; North, Kari E.; Laston, Sandra; Kooperberg, Charles; Avery, Christy L.

Evidence of Heterogeneity by Race/Ethnicity in Genetic Determinants of QT Interval

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  • Medientyp: E-Artikel
  • Titel: Evidence of Heterogeneity by Race/Ethnicity in Genetic Determinants of QT Interval
  • Beteiligte: Seyerle, Amanda A.; Young, Alicia M.; Jeff, Janina M.; Melton, Phillip E.; Jorgensen, Neal W.; Lin, Yi; Carty, Cara L.; Deelman, Ewa; Heckbert, Susan R.; Hindorff, Lucia A.; Jackson, Rebecca D.; Martin, Lisa W.; Okin, Peter M.; Perez, Marco V.; Psaty, Bruce M.; Soliman, Elsayed Z.; Whitsel, Eric A.; North, Kari E.; Laston, Sandra; Kooperberg, Charles; Avery, Christy L.
  • Erschienen: Lippincott Williams & Wilkins, Inc., 2014
  • Erschienen in: Epidemiology
  • Sprache: Englisch
  • ISSN: 1044-3983
  • Schlagwörter: Genetics
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <p>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 inversevariance 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 &lt; 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.</p>