TY - JOUR
T1 - Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease
AU - WTCCC+
AU - Huertas-Vazquez, Adriana
AU - Nelson, Christopher P.
AU - Guo, Xiuqing
AU - Reinier, Kyndaron
AU - Uy-Evanado, Audrey
AU - Teodorescu, Carmen
AU - Ayala, Jo
AU - Jerger, Katherine
AU - Chugh, Harpriya
AU - Braund, Peter S.
AU - Deloukas, Panos
AU - Hall, Alistair S.
AU - Balmforth, Anthony J.
AU - Jones, Michelle
AU - Taylor, Kent D.
AU - Pulit, Sara L.
AU - Newton-Cheh, Christopher
AU - Gunson, Karen
AU - Jui, Jonathan
AU - Rotter, Jerome I.
AU - Albert, Christine M.
AU - Samani, Nilesh J.
AU - Chugh, Sumeet S.
AU - Aerts, Jan
AU - Ahmad, Tariq
AU - Arbury, Hazel
AU - Attwood, Anthony
AU - Auton, Adam
AU - Ball, Stephen G.
AU - Balmforth, Anthony J.
AU - Barnes, Chris
AU - Barrett, Jeffrey C.
AU - Barroso, Inês
AU - Barton, Anne
AU - Bennett, Amanda J.
AU - Bhaskar, Sanjeev
AU - Blaszczyk, Katarzyna
AU - Bowes, John
AU - Brand, Oliver J.
AU - Braund, Peter S.
AU - Bredin, Francesca
AU - Breen, Gerome
AU - Brown, Morris J.
AU - Bruce, Ian N.
AU - Bull, Jaswinder
AU - Burren, Oliver S.
AU - Burton, John
AU - Byrnes, Jake
AU - Caesar, Sian
AU - Conrad, Donald F.
PY - 2013/4/4
Y1 - 2013/4/4
N2 - Background:Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).Methods and Findings:Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10-12, OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10-8, OR = 2.41).Conclusions:Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.
AB - Background:Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD).Methods and Findings:Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10-12, OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10-8, OR = 2.41).Conclusions:Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.
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U2 - 10.1371/journal.pone.0059905
DO - 10.1371/journal.pone.0059905
M3 - Article
C2 - 23593153
AN - SCOPUS:84875921005
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 4
M1 - e59905
ER -