4.7 Article

GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals

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SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-017-17136-0

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资金

  1. National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]
  2. University of Miami [N01-HC65234]
  3. Albert Einstein College of Medicine [N01-HC65235]
  4. Northwestern University [N01-HC65236]
  5. San Diego State University [N01-HC65237]
  6. NHLBI
  7. NIDCR [HHSN268201300005C AM03, MOD03]
  8. NHLBI HSN [26220/20054C]
  9. NCATS CTSI [UL1TR000124]
  10. NIDDK Diabetes Research Center (DRC) [DK063491]
  11. NHLBI [T32HL7055, T32HL07779, N02-HL-6-4278]
  12. Multi-Ethnic Study of Atherosclerosis (MESA) [HHSN2682015000031, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]
  13. NCRR [UL1-TR-000040, UL1-TR-001079, UL1-RR-025005]
  14. National Center for Advancing Translational Sciences, CTSI [UL1TR000124]
  15. National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]
  16. National Institutes of Health [DK073541, DK020595, AI085014, DK085501, HL102830]
  17. University of Texas Health Science Center at Houston
  18. National Institutes of Health (NIH) [HHSN268200782096C]
  19. National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]
  20. [R01HL116747]
  21. [R01 HL111089]

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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

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