Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10-10). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

doi.org/10.1371/journal.pgen.1002158, hdl.handle.net/1765/34500
P L o S Genetics (Print)
Erasmus MC: University Medical Center Rotterdam

Arking, D., Junttila, J., Goyette, P., Huertas-Vazquez, A., Eijgelsheim, M., Blom, M., … Chugh, S. (2011). Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals. P L o S Genetics (Print), 7(6). doi:10.1371/journal.pgen.1002158