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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
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Published in PLOS Genetics. 2011, vol. 7, no. 6, p. e1002158
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).
Keywords AdultAgedAllelesChromosomes, Human, Pair 2/geneticsDeath, Sudden, CardiacEuropean Continental Ancestry Group/geneticsFemaleGenetic Loci/geneticsGenetic Predisposition to Disease/geneticsGenome-Wide Association StudyHumansMaleMiddle AgedMyocardial Contraction/geneticsPolymorphism, Single Nucleotide/genetics
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PMID: 21738491
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Research group Traits génétiques complexes (901)
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ARKING, Dan E et al. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. In: PLOS Genetics, 2011, vol. 7, n° 6, p. e1002158. https://archive-ouverte.unige.ch/unige:32739

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Deposited on : 2014-01-02

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