PLoS Genetics (Jun 2011)

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

  • Dan E Arking,
  • M Juhani Junttila,
  • Philippe Goyette,
  • Adriana Huertas-Vazquez,
  • Mark Eijgelsheim,
  • Marieke T Blom,
  • Christopher Newton-Cheh,
  • Kyndaron Reinier,
  • Carmen Teodorescu,
  • Audrey Uy-Evanado,
  • Naima Carter-Monroe,
  • Kari S Kaikkonen,
  • Marja-Leena Kortelainen,
  • Gabrielle Boucher,
  • Caroline Lagacé,
  • Anna Moes,
  • XiaoQing Zhao,
  • Frank Kolodgie,
  • Fernando Rivadeneira,
  • Albert Hofman,
  • Jacqueline C M Witteman,
  • André G Uitterlinden,
  • Roos F Marsman,
  • Raha Pazoki,
  • Abdennasser Bardai,
  • Rudolph W Koster,
  • Abbas Dehghan,
  • Shih-Jen Hwang,
  • Pallav Bhatnagar,
  • Wendy Post,
  • Gina Hilton,
  • Ronald J Prineas,
  • Man Li,
  • Anna Köttgen,
  • Georg Ehret,
  • Eric Boerwinkle,
  • Josef Coresh,
  • W H Linda Kao,
  • Bruce M Psaty,
  • Gordon F Tomaselli,
  • Nona Sotoodehnia,
  • David S Siscovick,
  • Greg L Burke,
  • Eduardo Marbán,
  • Peter M Spooner,
  • L Adrienne Cupples,
  • Jonathan Jui,
  • Karen Gunson,
  • Y Antero Kesäniemi,
  • Arthur A M Wilde,
  • Jean-Claude Tardif,
  • Christopher J O'Donnell,
  • Connie R Bezzina,
  • Renu Virmani,
  • Bruno H C H Stricker,
  • Hanno L Tan,
  • Christine M Albert,
  • Aravinda Chakravarti,
  • John D Rioux,
  • Heikki V Huikuri,
  • Sumeet S Chugh

DOI
https://doi.org/10.1371/journal.pgen.1002158
Journal volume & issue
Vol. 7, no. 6
p. e1002158

Abstract

Read online

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).