Common genetic variants, QT interval, and sudden cardiac death in a finnish population-based study

Peter A. Noseworthy, Aki S. Havulinna, Kimmo Porthan, Annukka M. Lahtinen, Antti Jula, Pekka J. Karhunen, Markus Perola, Lasse Oikarinen, Kimmo K. Kontula, Veikko Salomaa, Christopher Cheh Newton

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Background-Although sudden cardiac death (SCD) is heritable, its genetic underpinnings are poorly characterized. The QT interval appears to have a graded relationship to SCD, and 35% to 45% of its variation is heritable. We examined the relationship among recently reported common genetic variants, QT interval, and SCD. Methods and Results-We genotyped 15 common (minor allele frequency >1%) candidate single nucleotide polymorphisms (SNPs), based on association with the QT interval in prior studies, in individuals in 2 cohort studies (Health 2000, n=6597; Mini-Finland, n=801). After exclusions, we identified 116 incident SCDs from the remaining sample (n=6808). We constructed a QT genotype score (QT score) using the allele copy number and previously reported effect estimates for each SNP. Cox proportional hazards models adjusting for age, sex, and geographical area were used for time to SCD analyses. The QT score was a continuous independent predictor of the heart rate-corrected QT interval (P=10 -107). Comparing the top with the bottom quintile of QT score, there was a 15.6-ms higher group mean QT interval (P=10 -84). A 10-ms increase in the observed QT interval was associated with an increased risk of SCD (hazard ratio, 1.19; 95% confidence interval, 1.07 to 1.32; P=0.002). There was no linear relationship between QT score and SCD risk; although in post hoc secondary analysis there was increased risk in the top compared with the middle QT score quintile (hazard ratio, 1.92; 95% confidence interval, 1.05 to 3.58; P=0.04). Conclusions-Our study strongly replicates the relationship between common genetic variants and the QT interval and confirms the relationship between the QT interval and SCD but does not show evidence for a linear relationship between QT score and SCD risk.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume4
Issue number3
DOIs
StatePublished - Jun 2011

Keywords

  • Death, sudden
  • Electrocardiography
  • Electrophysiology
  • Genetics
  • Mortality
  • QT interval

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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    Noseworthy, P. A., Havulinna, A. S., Porthan, K., Lahtinen, A. M., Jula, A., Karhunen, P. J., Perola, M., Oikarinen, L., Kontula, K. K., Salomaa, V., & Newton, C. C. (2011). Common genetic variants, QT interval, and sudden cardiac death in a finnish population-based study. Circulation: Cardiovascular Genetics, 4(3), 305-311. https://doi.org/10.1161/CIRCGENETICS.110.959049