title: Common genetic variants associated with sudden cardiac death: the FinSCDgen study.
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.
  
  
  RESULTS
  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<0.05).
  
  
  CONCLUSIONS
  Two novel genetic variants, one in the cardiac sodium channel gene SCN5A and another at 4q25 previously associated with atrial fibrillation, are associated with SCD.
authors: Research Programs Unit, Molecular Medicine and Department of Medicine, University of Helsinki, Helsinki, Finland.
authors: Annukka M
authors: AM
authors: Lahtinen
authors: Peter A
authors: PA
authors: Noseworthy
authors: Aki S
authors: AS
authors: Havulinna
authors: Antti
authors: A
authors: Jula
authors: Pekka J
authors: PJ
authors: Karhunen
authors: Johannes
authors: J
authors: Kettunen
authors: Markus
authors: M
authors: Perola
authors: Kimmo
authors: K
authors: Kontula
authors: Christopher
authors: C
authors: Newton-Cheh
authors: Veikko
authors: V
authors: Salomaa
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics; D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors