title: Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe.
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.
authors.affiliation: Departament Biologia Animal - Antropologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Carreras-Torres
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Suman
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Departament Biologia Animal - Antropologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zanetti
authors.affiliation: Departament Biologia Animal - Antropologia, Universitat de Barcelona, Barcelona, Spain; Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Esteban
authors.affiliation: Departament Psiquiatria i Psicobiologia Clínica and Institute for Brain, Cognition and Behaviour (IR3C), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Via
authors.affiliation: Departament Biologia Animal - Antropologia, Universitat de Barcelona, Barcelona, Spain; Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Moral
mesh_terms: D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D019001:Nitric Oxide Synthase