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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; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C M; Uitterlinden, André G; Marsman, Roos F; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W H Linda; Psaty, Bruce M; Tomaselli, Gordon F; Sotoodehnia, Nona; Siscovick, David S; Burke, Greg L; Marbán, Eduardo; Spooner, Peter M; Cupples, L Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y Antero; Wilde, Arthur A M; Tardif, Jean-Claude; O'Donnell, Christopher J; Bezzina, Connie R; Virmani, Renu; Stricker, Bruno H C H; Tan, Hanno L; Albert, Christine M; Chakravarti, Aravinda; Rioux, John D; Huikuri, Heikki V; Chugh, Sumeet S
- 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
PLoS genetics, 2011, Vol 7, Issue 6, pe1002158
- ISSN
1553-7404
- Publication type
Journal Article
- DOI
10.1371/journal.pgen.1002158