Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe.

Robert Carreras-Torres,Pedro Moral,Esther Esteban,Marc Via,Daniela Zanetti,Suman Kundu,Marie-Pierre Dubé

doi:10.1371/journal.pone.0096504

Robert Carreras-Torres, Pedro Moral + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0096504

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Journal: PloS one	Publication Date: May 7, 2014
Citations: 64	License type: CC BY 4.0

Affiliation: University of Barcelona, Erasmus MC

Abstract

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65–85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.

Highlights

The development of coronary artery diseases (CAD) is the result of complex interactions between numerous environmental factors and genetic variants at many loci
As for the data coming from the international project, genotyping status and imputation quality indexes are presented in Table S1 in File S1
The contribution of genetic risk scores (GRS) to CAD at the individual level was lower than 1%, GRS explained a large proportion of interpopulation differences in CAD incidence (65%–85%)

Summary

Introduction

The development of coronary artery diseases (CAD) is the result of complex interactions between numerous environmental factors and genetic variants at many loci. Epidemiologic research was largely based on cohort studies and clinical trials identifying and quantifying the relative importance of risk factors. As the World Health Organization (WHO) stated, the main identified risks for heart disease are behavioral factors: unhealthy diet, physical inactivity, tobacco use or harmful use of alcohol are present in about 80% of coronary events [1]. Different consortia had contributed to the development of estimation risk charts based on traditional risk factors (TRF), such as the Framingham Risk Score [2], the Reynolds Risk Score [3], the Prospective Cardiovascular Munster Heart Study (PROCAM) [4] and the Systematic Coronary Risk Evaluation (SCORE) system [5]. It has been estimated that nearly 15–20% of CAD patients are misclassified as ‘‘low risk’’ by TRF-based charts [7]

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