Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease

WTCCC+, Adriana Huertas-Vazquez, Christopher P. Nelson, Xiuqing Guo, Kyndaron Reinier, Audrey Uy-Evanado, Carmen Teodorescu, Jo Ayala, Katherine Jerger, Harpriya Chugh, Peter S. Braund, Panos Deloukas, Alistair S. Hall, Anthony J. Balmforth, Michelle Jones, Kent D. Taylor, Sara L. Pulit, Christopher Newton-Cheh, Karen Gunson, Jonathan Jui & 31 others Jerome I. Rotter, Christine M. Albert, Nilesh J. Samani, Sumeet S. Chugh, Jan Aerts, Tariq Ahmad, Hazel Arbury, Anthony Attwood, Adam Auton, Stephen G. Ball, Anthony J. Balmforth, Chris Barnes, Jeffrey C. Barrett, Inês Barroso, Anne Barton, Amanda J. Bennett, Sanjeev Bhaskar, Katarzyna Blaszczyk, John Bowes, Oliver J. Brand, Peter S. Braund, Francesca Bredin, Gerome Breen, Morris J. Brown, Ian N. Bruce, Jaswinder Bull, Oliver S. Burren, John Burton, Lynne Hocking, David M. Reid, D. St Clair

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Abstract

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.

Original languageEnglish
Article numbere59905
Number of pages6
JournalPloS ONE
Volume8
Issue number4
DOIs
Publication statusPublished - 4 Apr 2013

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Sudden Cardiac Death
Coronary Artery Disease
Genes
death
loci
Chromosomes
DNA
Chromosomes, Human, Pair 10
chromosomes
Chromosomes, Human, Pair 2
coronary artery disease
Genome-Wide Association Study
genes
Sudden Death
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease. / WTCCC+; Huertas-Vazquez, Adriana; Nelson, Christopher P.; Guo, Xiuqing; Reinier, Kyndaron; Uy-Evanado, Audrey; Teodorescu, Carmen; Ayala, Jo; Jerger, Katherine; Chugh, Harpriya; Braund, Peter S.; Deloukas, Panos; Hall, Alistair S.; Balmforth, Anthony J.; Jones, Michelle; Taylor, Kent D.; Pulit, Sara L.; Newton-Cheh, Christopher; Gunson, Karen; Jui, Jonathan; Rotter, Jerome I.; Albert, Christine M.; Samani, Nilesh J.; Chugh, Sumeet S.; Aerts, Jan; Ahmad, Tariq; Arbury, Hazel; Attwood, Anthony; Auton, Adam; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Chris; Barrett, Jeffrey C.; Barroso, Inês; Barton, Anne; Bennett, Amanda J.; Bhaskar, Sanjeev; Blaszczyk, Katarzyna; Bowes, John; Brand, Oliver J.; Braund, Peter S.; Bredin, Francesca; Breen, Gerome; Brown, Morris J.; Bruce, Ian N.; Bull, Jaswinder; Burren, Oliver S.; Burton, John; Hocking, Lynne; Reid, David M.; St Clair, D.

In: PloS ONE, Vol. 8, No. 4, e59905, 04.04.2013.

Research output: Contribution to journalArticle

WTCCC+, Huertas-Vazquez, A, Nelson, CP, Guo, X, Reinier, K, Uy-Evanado, A, Teodorescu, C, Ayala, J, Jerger, K, Chugh, H, Braund, PS, Deloukas, P, Hall, AS, Balmforth, AJ, Jones, M, Taylor, KD, Pulit, SL, Newton-Cheh, C, Gunson, K, Jui, J, Rotter, JI, Albert, CM, Samani, NJ, Chugh, SS, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Hocking, L, Reid, DM & St Clair, D 2013, 'Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease' PloS ONE, vol. 8, no. 4, e59905. https://doi.org/10.1371/journal.pone.0059905
WTCCC+ ; Huertas-Vazquez, Adriana ; Nelson, Christopher P. ; Guo, Xiuqing ; Reinier, Kyndaron ; Uy-Evanado, Audrey ; Teodorescu, Carmen ; Ayala, Jo ; Jerger, Katherine ; Chugh, Harpriya ; Braund, Peter S. ; Deloukas, Panos ; Hall, Alistair S. ; Balmforth, Anthony J. ; Jones, Michelle ; Taylor, Kent D. ; Pulit, Sara L. ; Newton-Cheh, Christopher ; Gunson, Karen ; Jui, Jonathan ; Rotter, Jerome I. ; Albert, Christine M. ; Samani, Nilesh J. ; Chugh, Sumeet S. ; Aerts, Jan ; Ahmad, Tariq ; Arbury, Hazel ; Attwood, Anthony ; Auton, Adam ; Ball, Stephen G. ; Balmforth, Anthony J. ; Barnes, Chris ; Barrett, Jeffrey C. ; Barroso, Inês ; Barton, Anne ; Bennett, Amanda J. ; Bhaskar, Sanjeev ; Blaszczyk, Katarzyna ; Bowes, John ; Brand, Oliver J. ; Braund, Peter S. ; Bredin, Francesca ; Breen, Gerome ; Brown, Morris J. ; Bruce, Ian N. ; Bull, Jaswinder ; Burren, Oliver S. ; Burton, John ; Hocking, Lynne ; Reid, David M. ; St Clair, D. / Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease. In: PloS ONE. 2013 ; Vol. 8, No. 4.
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title = "Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease",
abstract = "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.",
author = "WTCCC+ and Adriana Huertas-Vazquez and Nelson, {Christopher P.} and Xiuqing Guo and Kyndaron Reinier and Audrey Uy-Evanado and Carmen Teodorescu and Jo Ayala and Katherine Jerger and Harpriya Chugh and Braund, {Peter S.} and Panos Deloukas and Hall, {Alistair S.} and Balmforth, {Anthony J.} and Michelle Jones and Taylor, {Kent D.} and Pulit, {Sara L.} and Christopher Newton-Cheh and Karen Gunson and Jonathan Jui and Rotter, {Jerome I.} and Albert, {Christine M.} and Samani, {Nilesh J.} and Chugh, {Sumeet S.} and Jan Aerts and Tariq Ahmad and Hazel Arbury and Anthony Attwood and Adam Auton and Ball, {Stephen G.} and Balmforth, {Anthony J.} and Chris Barnes and Barrett, {Jeffrey C.} and In{\^e}s Barroso and Anne Barton and Bennett, {Amanda J.} and Sanjeev Bhaskar and Katarzyna Blaszczyk and John Bowes and Brand, {Oliver J.} and Braund, {Peter S.} and Francesca Bredin and Gerome Breen and Brown, {Morris J.} and Bruce, {Ian N.} and Jaswinder Bull and Burren, {Oliver S.} and John Burton and Lynne Hocking and Reid, {David M.} and {St Clair}, D.",
note = "The Oregon Sudden Unexpected Death Study acknowledges the significant contribution of American Medical Response and the Portland/Gresham fire Departments.",
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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 - Hocking, Lynne

AU - Reid, David M.

AU - St Clair, D.

N1 - The Oregon Sudden Unexpected Death Study acknowledges the significant contribution of American Medical Response and the Portland/Gresham fire Departments.

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

VL - 8

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 4

M1 - e59905

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