Journal article
GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals
Scientific reports, Vol.7(1), 17075
12/06/2017
DOI: 10.1038/s41598-017-17136-0
PMCID: PMC5719082
PMID: 29213071
Abstract
QT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured QT were combined using fixed-effects meta-analysis. We identified 41 genome-wide significant SNPs that mapped to 13 previously identified QT loci. Conditional analyses distinguished six secondary signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1). Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six secondary signals with previously reported index SNPs in 1000G super populations suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and population-specific. Finally, of the 42 suggestively associated loci, AJAP1 was suggestively associated with QT in a prior East Asian GWAS; in contrast BVES and CAP2 murine knockouts caused cardiac conduction defects. Our results indicate that whereas the same loci influence QT across populations, population-specific variation exists, motivating future trans-ethnic and ancestrally diverse QT GWAS.
Details
- Title: Subtitle
- GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals
- Creators
- Raúl Méndez-Giráldez - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. rmendez@email.unc.eduStephanie M Gogarten - Department of Biostatistics, University of Washington, Seattle, WA, USAJennifer E Below - The Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USAJie Yao - The Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USAAmanda A Seyerle - Division of Epidemiology and Community, University of Minnesota, Minneapolis, MN, USAHeather M Highland - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USACharles Kooperberg - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USAElsayed Z Soliman - Epidemiological Cardio Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USAJerome I Rotter - The Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USAKathleen F Kerr - Department of Biostatistics, University of Washington, Seattle, WA, USAKelli K Ryckman - Departments of Epidemiology and Pediatrics, University of Iowa, Iowa City, IA, USAKent D Taylor - The Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USALauren E Petty - Center for Precision Medicine, University of Texas, Health Science Center at Houston, Houston, TX, USASanjiv J Shah - Northwestern Memorial HospitalMatthew P Conomos - Department of Biostatistics, University of Washington, Seattle, WA, USANona Sotoodehnia - Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USASusan Cheng - Brigham and Women's HospitalSusan R Heckbert - Department of Epidemiology, University of Washington, Seattle, WA, USATamar Sofer - Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USAXiuqing Guo - The Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USAEric A Whitsel - Department of Medicine, University of North Carolina, Chapel Hill, NC, USACraig L Hanis - Human Genetics Center, University of Texas, Health Science Center at Houston, Houston, TX, USACathy C Laurie - Department of Biostatistics, University of Washington, Seattle, WA, USAHenry J Lin - Harbor–UCLA Medical CenterChristy L Avery - Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA. christy_avery@unc.edu
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), 17075
- DOI
- 10.1038/s41598-017-17136-0
- PMID
- 29213071
- PMCID
- PMC5719082
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Grant note
- N01HC65235 / NHLBI NIH HHS N01HC95169 / NHLBI NIH HHS N01HC95161 / NHLBI NIH HHS HHSN268201600003C / NHLBI NIH HHS UL1 TR001881 / NCATS NIH HHS T32 HL007779 / NHLBI NIH HHS N01HC95164 / NHLBI NIH HHS N01HC65237 / NHLBI NIH HHS N01HC95167 / NHLBI NIH HHS R01 HL111089 / NHLBI NIH HHS HHSN268200782096C / NHGRI NIH HHS HHSN268201600018C / NHLBI NIH HHS HHSN268201300005C / NHLBI NIH HHS N01HC95159 / NHLBI NIH HHS N01HC95163 / NHLBI NIH HHS N01HC95166 / NHLBI NIH HHS HHSN268201600002C / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS UL1 TR000124 / NCATS NIH HHS P2C HD050924 / NICHD NIH HHS UL1 RR025005 / NCRR NIH HHS HHSN268201600001C / NHLBI NIH HHS N01HC65234 / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS R01 HL116747 / NHLBI NIH HHS HHSN268201600004C / NHLBI NIH HHS N01HC65233 / NHLBI NIH HHS T32 HL007055 / NHLBI NIH HHS N01HC65236 / NHLBI NIH HHS N01HC95168 / NHLBI NIH HHS UL1 TR000040 / NCATS NIH HHS N01HC95165 / NHLBI NIH HHS P30 DK063491 / NIDDK NIH HHS N01HC95162 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/06/2017
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology
- Record Identifier
- 9983996068302771
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