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

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, Jerome I. RotterChristine 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, WTCCC+

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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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ASJC Scopus subject areas

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

Cite this

Huertas-Vazquez, A., Nelson, C. P., Guo, X., Reinier, K., Uy-Evanado, A., Teodorescu, C., ... WTCCC+ (2013). Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease. PloS ONE, 8(4), [e59905]. https://doi.org/10.1371/journal.pone.0059905