TY - JOUR
T1 - Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals
AU - Arking, Dan E.
AU - Junttila, M. Juhani
AU - Goyette, Philippe
AU - Huertas-Vazquez, Adriana
AU - Eijgelsheim, Mark
AU - Blom, Marieke T.
AU - Newton-Cheh, Christopher
AU - Reinier, Kyndaron
AU - Teodorescu, Carmen
AU - Uy-Evanado, Audrey
AU - Carter-Monroe, Naima
AU - Kaikkonen, Kari S.
AU - Kortelainen, Marja Leena
AU - Boucher, Gabrielle
AU - Lagacé, Caroline
AU - Moes, Anna
AU - Zhao, Xiao Qing
AU - Kolodgie, Frank
AU - Rivadeneira, Fernando
AU - Hofman, Albert
AU - Witteman, Jacqueline C.M.
AU - Uitterlinden, André G.
AU - Marsman, Roos F.
AU - Pazoki, Raha
AU - Bardai, Abdennasser
AU - Koster, Rudolph W.
AU - Dehghan, Abbas
AU - Hwang, Shih Jen
AU - Bhatnagar, Pallav
AU - Post, Wendy
AU - Hilton, Gina
AU - Prineas, Ronald J.
AU - Li, Man
AU - Köttgen, Anna
AU - Ehret, Georg
AU - Boerwinkle, Eric
AU - Coresh, Josef
AU - Kao, W. H.Linda
AU - Psaty, Bruce M.
AU - Tomaselli, Gordon F.
AU - Sotoodehnia, Nona
AU - Siscovick, David S.
AU - Burke, Greg L.
AU - Marbán, Eduardo
AU - Spooner, Peter M.
AU - Cupples, L. Adrienne
AU - Jui, Jonathan
AU - Gunson, Karen
AU - Kesäniemi, Y. Antero
AU - Wilde, Arthur A.M.
AU - Tardif, Jean Claude
AU - O'Donnell, Christopher J.
AU - Bezzina, Connie R.
AU - Virmani, Renu
AU - Stricker, Bruno H.C.h.
AU - Tan, Hanno L.
AU - Albert, Christine M.
AU - Chakravarti, Aravinda
AU - Rioux, John D.
AU - Huikuri, Heikki V.
AU - Chugh, Sumeet S.
PY - 2011/6
Y1 - 2011/6
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=79959854942&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pgen.1002158
DO - https://doi.org/10.1371/journal.pgen.1002158
M3 - Article
C2 - 21738491
SN - 1553-7390
VL - 7
SP - e1002158
JO - PLoS genetics
JF - PLoS genetics
IS - 6
M1 - e1002158
ER -