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- Title
Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals.
- Authors
Arking, Dan E.; Junttila, M. Juhani; Goyette, Philippe; Huertas-Vazquez, Adriana; Eijgelsheim, Mark; Blom, Marieke T.; Newton-Cheh, Christopher; Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; XiaoQing Zhao; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert
- Abstract
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 = 1.8x10-10 ). 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 intervalprolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).
- Subjects
CARDIAC arrest; GENETICS of disease susceptibility; MORTALITY; META-analysis; DISEASE incidence; ELECTROCARDIOGRAPHY; GENETIC epidemiology
- Publication
PLoS Genetics, 2011, Vol 7, Issue 6, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1002158