Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease

Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD. We genotyp...

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Vydáno v:Arteriosclerosis, thrombosis, and vascular biology Ročník 33; číslo 9; s. 2261
Hlavní autoři: Tikkanen, Emmi, Havulinna, Aki S, Palotie, Aarno, Salomaa, Veikko, Ripatti, Samuli
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.09.2013
Témata:
Adult
Coronary Disease - classification
Coronary Disease - diagnosis
Coronary Disease - epidemiology
Coronary Disease - genetics
Coronary Disease - prevention & control
Disease Progression
Female
Finland - epidemiology
Gene Frequency
Genetic Predisposition to Disease
Genetic Testing
Genome-Wide Association Study
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Linear Models
Male
Mass Screening - methods
Middle Aged
Molecular Epidemiology
Patient Selection
Phenotype
Polymorphism, Single Nucleotide
Predictive Value of Tests
Prevalence
Preventive Health Services
Prognosis
Proportional Hazards Models
Prospective Studies
Risk Assessment
Risk Factors
Time Factors
Finland
genetic association
cardiovascular genomics
risk factor
risk prediction
genetic epidemiology
ISSN:1524-4636, 1524-4636
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Shrnutí:Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD. We genotyped 28 genetic variants in 24 124 participants in 4 Finnish population-based, prospective cohorts (recruitment years 1992-2002). We constructed a multilocus genetic risk score and evaluated its association with incident cardiovascular disease events. During the median follow-up time of 12 years (interquartile range 8.75-15.25 years), we observed 1093 CHD, 1552 cardiovascular disease, and 731 acute coronary syndrome events. Adding genetic information to conventional risk factors and family history improved risk discrimination of CHD (C-index 0.856 versus 0.851; P=0.0002) and other end points (cardiovascular disease: C-index 0.840 versus 0.837, P=0.0004; acute coronary syndrome: C-index 0.859 versus 0.855, P=0.001). In a standard population of 100 000 individuals, additional genetic screening of subjects at intermediate risk for CHD would reclassify 2144 subjects (12%) into high-risk category. Statin allocation for these subjects is estimated to prevent 135 CHD cases over 14 years. Similar results were obtained by external validation, where the effects were estimated from a training data set and applied for a test data set. Genetic risk score improves risk prediction of CHD and helps to identify individuals at high risk for the first CHD event. Genetic screening for individuals at intermediate cardiovascular risk could help to prevent future cases through better targeting of statins.
Bibliografie:ObjectType-Article-1
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ISSN:1524-4636
1524-4636
DOI:10.1161/ATVBAHA.112.301120