Abstract 17170: Common Single Nucleotide Polymorphisms Associated with Sudden Cardiac Death: The FinSCDgen Study
Introduction: Sudden cardiac death (SCD) comprises about 15% of all deaths in western countries and about two thirds of all cardiac deaths. It is known to be heritable but the underlying genetic variants are poorly known.
Hypothesis: We hypothesized that common genetic variants associated with QT interval, arrhythmias and other cardiac phenotypes, would also be associated with SCD.
Methods: We genotyped 36 common (minor allele frequency >1%) candidate SNPs in four Finnish cohort studies (FINRISK 1992, 1997, 2002 and Health 2000, total n=26,337, followed up until the end of 2007, and two series of forensic autopsies (combined n=695). Persons aged < 25 or > 80 years at the time of death were excluded. The adjudication process revealed 717 probable or possible SCDs. Cox proportional hazard regression was used for analyzing the SCD risk in FINRISK and Health 2000 cohorts and logistic regression was used in the forensic autopsy studies for computing the odds ratios comparing the SCDs with other autopsied sudden deaths in the same population and the same year. The primary models were adjusted for age and sex and geographical area. In prospective analyses additional models adjusted for conventional cardiovascular risk factors and the presence of coronary heart disease (CHD) before death. The risk estimates were pooled using inverse variance weighted, fixed effects meta-analysis.
Results: As expected, male gender, systolic blood pressure, diabetes, smoking (current and former) and presence of CHD were significantly associated with increased risk of SCD, whereas regular leisure time physical activity was protective. Genetic analyses revealed 5 SNPs significantly associated with SCD at the p<0.05 level. The strongest associations included rs2200733 on chr4q25, previously related to atrial fibrillation risk, with a relative risk of 1.23 (95% CI 1.06 - 1.42., p=0.006) per copy of minor allele and rs41312391 in an intron of SCN5A,with RR of 1.25 (95% CI 1.10-1.43, p=0.001).
Conclusions: Our study identifies novel genetic variants associated with the risk of SCD. The magnitude of the risk was, however, modest compared with the effects of the established clinical factors. Larger studies are warranted to fully define the contribution of common genetic factors to SCD.
- © 2010 by American Heart Association, Inc.