Each increasing copy of the G allele at rs10757274 on chromosome 9p21 was associated with an increased risk of sudden cardiac death (OR 1.29; 95% CI 1.09-1.53; P=0.003).
Case-Control (n=1,952)
Yes
Does the common variant at chromosome 9p21 (rs10757274) increase the risk of sudden cardiac death in individuals of European ancestry?
The common genetic variant at chromosome 9p21 (rs10757274), previously linked to coronary artery disease, is also associated with an increased risk of sudden cardiac death in individuals of European ancestry.
Effect estimate: OR 1.29 (95% CI 1.09-1.53)
p-value: p=0.003
BACKGROUND: Although a heritable basis for sudden cardiac death (SCD) is suggested by the impact of family history on SCD risk, common genetic determinants have been difficult to identify. We hypothesized that a common variant at chromosome 9p21 related to myocardial infarction would influence SCD risk. METHODS AND RESULTS: This was a prospective, nested, case-control analysis among individuals of European ancestry enrolled in 6 prospective cohort studies. Study subjects were followed up for development of SCD, and genotypes for rs10757274 were determined for 492 sudden and/or arrhythmic deaths and 1460 controls matched for age, sex, cohort, history of cardiovascular disease, and follow-up time. Conditional logistic regression with fixed-effects meta-analysis assuming an additive model was used to test for associations. When individual study results were combined in the meta-analysis, each increasing copy of the G allele at rs10757274 conferred a significantly elevated age-adjusted odds ratio for SCD of 1.21 (95% confidence interval, 1.04 to 1.40; P=0.01). Controlling for cardiovascular and lifestyle risk factors strengthened these relationships (odds ratio, 1.29 per G-allele copy; 95% confidence interval, 1.09 to 1.53; P=0.003). These results were not materially altered in sensitivity analyses limited to definite SCD, in models that further controlled for the development of interim cardiovascular disease, or when the highly correlated variant rs2383207 was tested. CONCLUSIONS: The major allele of a single-nucleotide polymorphism previously associated with increased risk of coronary artery disease events is associated with increased risk of SCD in individuals of European ancestry. Study of the mechanism underlying this association may improve our understanding of lethal cardiovascular disease.
Newton‐Cheh et al. (Tue,) conducted a case-control in Sudden cardiac death (n=1,952). G allele at rs10757274 (chromosome 9p21) vs. Matched controls was evaluated on Sudden cardiac death (OR 1.29, 95% CI 1.09-1.53, p=0.003). Each increasing copy of the G allele at rs10757274 on chromosome 9p21 was associated with an increased risk of sudden cardiac death (OR 1.29; 95% CI 1.09-1.53; P=0.003).
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