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Title: Cumulative effects of common genetic variants on risk of sudden cardiac death.
Authors: Huertas-Vazquez, A.
Nelson, Christopher P.
Sinsheimer, J. S.
Reinier, K.
Uy-Evanado, A.
Teodorescu, C.
Ayala, J.
Hall, A. S.
Gunson, K.
Jui, J.
Samani, Nilesh J.
Chugh, S. S.
First Published: 7-Mar-2015
Publisher: Elsevier Ireland Ltd.
Citation: IJC Heart & Vasculature, 2015, 7, pp. 88-91
Abstract: Background Genome-wide association studies and candidate-gene based approaches have identified multiple common variants associated with increased risk of sudden cardiac death (SCD). However, the independent contribution of these individual loci to disease risk is modest. Objective To investigate the cumulative effects of genetic variants previously associated with SCD risk. Methods A total of 966 SCD cases from the Oregon-Sudden Unexpected Death Study and 1926 coronary artery disease controls from the Wellcome Trust Case–Control Consortium were investigated. We generated genetic risk scores (GRSs) for each trait composed of variants previously associated with SCD or with abnormalities in specific electrocardiographic traits such as QRS duration, QTc interval and heart rate. GRSs were calculated using a weighted approach based on the number of risk alleles weighted by the beta coefficients derived from the original studies. We also compared the highest and lowest quintiles for the GRS composed of SCD SNPs. Results Increased cumulative risk was observed for a GRS composed of 14 SCD-SNPs (OR = 1.17 [1.05–1.29], P = 0.002). The risk for SCD was 1.5 fold greater in the highest risk quintile when compared to the lowest risk quintile (OR = 1.46 [1.11–1.92]). We did not observe significant associations with SCD for SNPs that determine electrocardiographic traits. Conclusions A modest but significant effect on SCD risk was identified for a GRS composed of 14 previously associated SCD SNPs. While next generation sequencing methodology will continue to identify additional novel variants, these findings represent proof of concept for the additive effects of gene variants on SCD risk.
DOI Link: 10.1016/j.ijcha.2015.03.001
ISSN: 2352-9067
eISSN: 2352-9067
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2015 The Authors. Published by Elsevier Ireland Ltd.This is an open access article under the CC BY-NC-ND license (
Description: PMCID: PMC4476546
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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