title: Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval.
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'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.
authors.affiliation: From the aDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC; bDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; cCharles Bronfman Institute of Personalized Medicine, Mount Sinai School of Medicine, New York, NY; dCentre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Australia; eDepartment of Biostatistics, University of Washington, Seattle, WA; fInformation Sciences Institute and Computer Science Department, University of Southern California, Marina Del Rey, CA; gDepartment of Epidemiology, University of Washington, Seattle, WA; hCardiovascular Health Research Unit, University of Washington, Seattle, WA; iGroup Health Research Institute, Group Health Cooperative, Seattle, WA; jOffice of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; kDepartment of Internal Medicine, Ohio State Medical Center, Columbus, OH; lDivision of Cardiology, George Washington University, Washington, DC; mDepartment of Medicine, Weill Cornell Medical College, New York, NY; nDivision of Cardiovascular Medicine, Stanford University, Stanford, CA; oDivision of Medicine, University of Washington, Seattle, WA; pDivision of Health Services, University of Washington, Seattle, WA; qEpidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston-Salem, NC; rDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; and sDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Seyerle
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Young
authors.forename: Janina M
authors.initials: JM
authors.lastname: Jeff
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Melton
authors.forename: Neal W
authors.initials: NW
authors.lastname: Jorgensen
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Cara L
authors.initials: CL
authors.lastname: Carty
authors.forename: Ewa
authors.initials: E
authors.lastname: Deelman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Peter M
authors.initials: PM
authors.lastname: Okin
authors.forename: Marco V
authors.initials: MV
authors.lastname: Perez
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: Eric A
authors.initials: EA
authors.lastname: Whitsel
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Sandra
authors.initials: S
authors.lastname: Laston
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Christy L
authors.initials: CL
authors.lastname: Avery
mesh_terms: D000368:Aged; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008133:Long QT Syndrome / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D044469:Racial Groups / Q000235:genetics*; D012307:Risk Factors