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Additive effect of multiple genetic variants on the risk of coronary artery disease
Carla Lluís-Ganella1, Gavin Lucas, Isaac Subirana
1Grupo de Epidemiología y Genética Cardiovascular ULEC, Institut Municipal d'Investigació Mèdica, Hospital del Mar, Barcelona, España.
Insights
A genetic risk score, using nine variants, significantly correlates with coronary artery disease (CAD) presence. This score, based on accumulated risk alleles, shows a linear association with CAD risk, highlighting genetic factors in heart disease.
Area of Science:
- Cardiovascular Genetics
- Genomic Epidemiology
- Disease Risk Prediction
Background:
- Coronary artery disease (CAD) possesses a significant genetic component, with numerous associated genetic variants identified.
- Understanding the genetic architecture of CAD is crucial for improving risk assessment and patient outcomes.
Purpose of the Study:
- To evaluate the association between a genetic risk score and the presence of coronary artery disease (CAD).
- To quantify the predictive power of accumulated risk alleles for CAD development.
Main Methods:
- Utilized in silico data from the Wellcome Trust Case-Control Consortium, including 1988 CAD patients and 5380 controls.
- Employed logistic regression analysis to assess the association between the genetic risk score and CAD presence.
Main Results:
- Identified nine genetic variants independently associated with CAD, regardless of other cardiovascular risk factors.
- Demonstrated a significant linear association between the number of risk alleles and CAD risk (OR=1.18 per allele, P=2x10⁻¹⁶).
- The highest quintile of risk alleles showed a 2.21-fold increased odds of CAD compared to the lowest quintile (P=5x10⁻²¹).
Conclusions:
- A genetic risk score incorporating nine key variants is associated with the presence of CAD.
- Further cohort studies are warranted to determine if this genetic risk score enhances the predictive capacity of existing cardiovascular risk models.
Introduction And Objectives:
Coronary artery disease (CAD) has a substantial genetic component and, in recent years, a number of genetic variants associated with the disease have been identified. The objective of this study was to evaluate the magnitude of the association between a genetic risk score, which is based on the accumulated number of risk alleles in all genetic variants of interest, and the presence of CAD.
Methods:
The study involved in silico data from the Wellcome Trust Case-Control Consortium on 1988 patients with CAD and 5380 controls. The association between the genetic risk score and CAD was assessed using logistic regression analysis.
Results:
Nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors were selected. There was a linear association between the number of risk alleles and the risk of presenting with CAD (odds ratio [OR] for an increase of one allele=1.18; 95% confidence interval [CI], 1.15-1.22; P=2 x 10-16). The OR for CAD for the last quintile of the accumulated number of risk alleles relative to the first was 2.21 (95%CI, 1.87-2.61; P=5 x 10-21).
Conclusions:
A genetic risk score based on nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors was associated with the presence of the disease. Cohort studies are needed to determine whether this genetic risk score can improve the predictive capacity or the risk classification of classical risk functions.
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