Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals

PLoS Genet. 2011 Jun;7(6):e1002158. doi: 10.1371/journal.pgen.1002158. Epub 2011 Jun 30.

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Chromosomes, Human, Pair 2 / genetics*
  • Death, Sudden, Cardiac*
  • European Continental Ancestry Group / genetics*
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Contraction / genetics
  • Polymorphism, Single Nucleotide / genetics

Grant support