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Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.
- Source :
-
PLoS genetics [PLoS Genet] 2011 Jun; Vol. 7 (6), pp. e1002158. Date of Electronic Publication: 2011 Jun 30. - Publication Year :
- 2011
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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).<br />Competing Interests: AC is a paid member of the Scientific Advisory Board of Affymetrix, a role that is managed by the Committee on Conflict of Interest of the Johns Hopkins University School of Medicine.
- Subjects :
- Adult
Aged
Alleles
Female
Humans
Male
Middle Aged
Myocardial Contraction genetics
Polymorphism, Single Nucleotide genetics
Chromosomes, Human, Pair 2 genetics
Death, Sudden, Cardiac
Genetic Loci genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 7
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 21738491
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002158