title: From candidate gene to genome-wide association studies in cardiovascular disease.
abstract: Continuous updating of the genotyping technology has led to improvement of genetic study design. The recent advances in technology coupled with the advances in our understanding of the molecular mechanisms have allowed a more comprehensive examination of the role of genetics, environment and their interaction in determining the individual risk of cardiovascular disease (CVD). Initial candidate gene studies identified a limited number of polymorphisms associated with disease, explaining only a minor part of trait variance. Furthermore, results were not often concordant, with meta-analyses not reaching the statistical power to confirm an association in many cases. The advent of the genome-wide design furnished an enormous quantity of information and decreased time of genotyping, while increased complexity of analyses and costs. Their results were more concordant, even when they suggested associations between CVD and polymorphisms distant from codifying regions or in genes involved in previously unsuspected pathways. Future results from genome-wide studies coupled with results from functional studies and investigation on gene-environment interactions will allow improvement of cardiovascular risk assessment and discovery of new targets for therapy and prevention. In this review, a brief history of cardiovascular genetics is reported, from candidate gene to genome wide association studies, that led to the identification of association between CVD and SNPs in the 9p21 region, firstly thought a gene desert without importance.
authors.affiliation: Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gianfagna
authors.forename: Daniela
authors.initials: D
authors.lastname: Cugino
authors.forename: Iolanda
authors.initials: I
authors.lastname: Santimone
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000266:history / Q000628:therapy; D019317:Evidence-Based Medicine; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies / Q000266:history; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D055106:Genome-Wide Association Study / Q000266:history; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D012307:Risk Factors