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Public Library of Science, PLoS Genetics, 6(7), p. e1002158, 2011

DOI: 10.1371/journal.pgen.1002158

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Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Journal article published in 2011 by Dan E. (Dan) Arking, M. Juhani Junttila, M. Juhani Junttila, Philippe Goyette, Adriana Huertas-Vazquez, Mark Eijgelsheim, Marieke T. (Marieke) Blom, Christopher Newton-Cheh, Kyndaron Reinier, Carmen Teodorescu, Audrey Uy-Evanado, Naima Carter-Monroe, Kari S. (Kari) Kaikkonen, Marja-Leena Kortelainen, Gabrielle Boucher and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 = 1.8×10(-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).