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, Xiao Qing Zhao, Frank Kolodgie, Fernando Rivadeneira, Albert HofmanJacqueline 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

Research output: Contribution to journalArticle

91 Scopus citations

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).

Original languageEnglish (US)
Article numbere1002158
JournalPLoS genetics
Volume7
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Arking, D. E., Junttila, M. J., Goyette, P., Huertas-Vazquez, A., Eijgelsheim, M., Blom, M. T., Newton-Cheh, C., Reinier, K., Teodorescu, C., Uy-Evanado, A., Carter-Monroe, N., Kaikkonen, K. S., Kortelainen, M. L., Boucher, G., Lagacé, C., Moes, A., Zhao, X. Q., Kolodgie, F., Rivadeneira, F., ... Chugh, S. S. (2011). Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals. PLoS genetics, 7(6), [e1002158]. https://doi.org/10.1371/journal.pgen.1002158