Related Experiment Video
Updated: Apr 14, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Predicting sudden cardiac death using common genetic risk variants for coronary artery disease
Jussi A Hernesniemi1, Leo-Pekka Lyytikäinen2, Niku Oksala3
1Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland North Karelia Central Hospital, Tikkamäentie 16, Joensuu 80210, Finland jussi.hernesniemi@uta.fi.
Aims:
Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD).
Methods And Results:
A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)].
Conclusion:
Genetic risk estimate for CAD may also be used to predict SCD.
More Related Videos
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
06:16Signal Acquisition, Score Interpretation, and Economics of a Non-Invasive Point-of-Care Test for Coronary Artery Disease
Published on: August 9, 2024
Related Concept Videos
Coronary Artery Disease I: Introduction
Coronary Artery Disease III: Clinical Manifestations
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Pharmacogenomics: Identification of New Drug Targets
Cardiomyopathy III: Hypertrophic Cardiomyopathy
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu