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

TitleIdentification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.
Publication TypeJournal Article
Year of Publication2011
AuthorsArking DE, M Junttila J, Goyette P, Huertas-Vazquez A, Eijgelsheim M, Blom MT, Newton-Cheh C, Reinier K, Teodorescu C, Uy-Evanado A, Carter-Monroe N, Kaikkonen KS, Kortelainen M-L, Boucher G, Lagacé C, Moes A, Zhao XQ, Kolodgie F, Rivadeneira F, Hofman A, Witteman JCM, Uitterlinden AG, Marsman RF, Pazoki R, Bardai A, Koster RW, Dehghan A, Hwang S-J, Bhatnagar P, Post W, Hilton G, Prineas RJ, Li M, Köttgen A, Ehret G, Boerwinkle E, Coresh J, Kao LWH, Psaty BM, Tomaselli GF, Sotoodehnia N, Siscovick DS, Burke GL, Marbán E, Spooner PM, L Cupples A, Jui J, Gunson K, Y Kesäniemi A, Wilde AAM, Tardif J-C, O'Donnell CJ, Bezzina CR, Virmani R, Stricker BHCH, Tan HL, Albert CM, Chakravarti A, Rioux JD, Huikuri HV, Chugh SS
JournalPLoS Genet
Volume7
Issue6
Paginatione1002158
Date Published2011 Jun
ISSN1553-7404
KeywordsAdult, Aged, Alleles, Chromosomes, Human, Pair 2, Death, Sudden, Cardiac, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Myocardial Contraction, Polymorphism, Single Nucleotide
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).

DOI10.1371/journal.pgen.1002158
Alternate JournalPLoS Genet
PubMed ID21738491
PubMed Central IDPMC3128111
Grant ListUL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
CA-34944 / CA / NCI NIH HHS / United States
HL-34595 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
HL-46959 / HL / NHLBI NIH HHS / United States
N01-HC-80007 / HC / NHLBI NIH HHS / United States
HL-26490 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
R01 HL105170-01 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
CA 97193 / CA / NCI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
R01 HL088416 / HL / NHLBI NIH HHS / United States
R01 HL034595 / HL / NHLBI NIH HHS / United States
CA-87969 / CA / NCI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
CA55075 / CA / NCI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
HL-34594 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
CA 40360 / CA / NCI NIH HHS / United States
R01 HL046959 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
R01 HL034594 / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
R01 HL068070 / HL / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R01 HL088416-03S1 / HL / NHLBI NIH HHS / United States
R01 HL026490 / HL / NHLBI NIH HHS / United States
HL-080467 / HL / NHLBI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
1UL1RR025005 / RR / NCRR NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL035464 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 CA040360 / CA / NCI NIH HHS / United States
HL-35464 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HL068070 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 CA097193 / CA / NCI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R01 CA034944 / CA / NCI NIH HHS / United States
R01 HL091069 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01 HL105170 / HL / NHLBI NIH HHS / United States