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Common Genetic Variants Associated with Sudden Cardiac Death: The FinSCDgen Study

Author

Listed:
  • Annukka M Lahtinen
  • Peter A Noseworthy
  • Aki S Havulinna
  • Antti Jula
  • Pekka J Karhunen
  • Johannes Kettunen
  • Markus Perola
  • Kimmo Kontula
  • Christopher Newton-Cheh
  • Veikko Salomaa

Abstract

Background: Sudden cardiac death (SCD) accounts for up to half of cardiac mortality. The risk of SCD is heritable but the underlying genetic variants are largely unknown. We investigated whether common genetic variants predisposing to arrhythmia or related electrocardiographic phenotypes, including QT-interval prolongation, are associated with increased risk of SCD. Methodology/Principal Findings: We studied the association between 28 candidate SNPs and SCD in a meta-analysis of four population cohorts (FINRISK 1992, 1997, 2002 and Health 2000, n = 27,629) and two forensic autopsy series (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 694). We also studied the association between established cardiovascular risk factors and SCD. Causes of death were reviewed using registry-based health and autopsy data. Cox regression and logistic regression models were adjusted for age, sex, and geographic region. The total number of SCDs was 716. Two novel SNPs were associated with SCD: SCN5A rs41312391 (relative risk [RR] 1.27 per minor T allele, 95% CI 1.11–1.45, P = 3.4×10−4) and rs2200733 in 4q25 (RR 1.28 per minor T allele, 95% CI 1.11–1.48, P = 7.9×10−4). We also replicated the associations for 9p21 (rs2383207, RR 1.13 per G allele, 95% CI 1.01–1.26, P = 0.036), as well as for male sex, systolic blood pressure, diabetes, cigarette smoking, low physical activity, coronary heart disease, and digoxin use (P

Suggested Citation

  • Annukka M Lahtinen & Peter A Noseworthy & Aki S Havulinna & Antti Jula & Pekka J Karhunen & Johannes Kettunen & Markus Perola & Kimmo Kontula & Christopher Newton-Cheh & Veikko Salomaa, 2012. "Common Genetic Variants Associated with Sudden Cardiac Death: The FinSCDgen Study," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-7, July.
    • Handle: RePEc:plo:pone00:0041675
    DOI: 10.1371/journal.pone.0041675
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    References listed on IDEAS

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    1. Axel Visel & Yiwen Zhu & Dalit May & Veena Afzal & Elaine Gong & Catia Attanasio & Matthew J. Blow & Jonathan C. Cohen & Edward M. Rubin & Len A. Pennacchio, 2010. "Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice," Nature, Nature, vol. 464(7287), pages 409-412, March.
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    Cited by:

    1. Miikka Korja & Karri Silventoinen & Tiina Laatikainen & Pekka Jousilahti & Veikko Salomaa & Juha Hernesniemi & Jaakko Kaprio, 2013. "Risk Factors and Their Combined Effects on the Incidence Rate of Subarachnoid Hemorrhage – A Population-Based Cohort Study," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-7, September.

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