Genetisch model voorspelt 10-jaars CHD risico

Nieuws - Oct. 26, 2010

Genetic model predicts 10-year CHD event risk

26 October 2010

Individuals with an elevated risk for first coronary heart disease (CHD) event can be identified using a genetic risk score based on 13 single nucleotide polymorphisms (SNPs), study results show.

However, the genetic score did not add any additional predictive value above that of traditional risk factors, report Samuli Ripatti (University of Helsinki, Finland) and colleagues in the Lancet. Indeed, they write: "These results emphasize the challenge of risk prediction for complex traits on the basis of any single factor."

A family history of premature CHD is an independent risk factor for first CHD event, suggesting that inherited DNA sequence variants contribute to risk of the disease.

So far, genome-wide association studies using case-control designs have identified SNPs at 13 genomic regions, which are significantly associated with CHD, myocardial infarction, or both.

However these "discovery" studies have ascertained cases on the basis of early age of disease onset or affected family members, and as such the reported effect estimates might not be representative of the general population, Ripatti et al argue.

The researchers therefore set out to determine, firstly, if these reported genetic associations could be externally validated in a independent case-control cohort and, secondly, if precise risk estimates could be obtained with a prospective cohort design - the "gold standard" in epidemiologic investigations.

The validation study comprised 3829 participants with prevalent CHD and 48,897 controls free of the disease drawn from seven cohorts: the FINRISK 1992, 1997, and 2002; Health 2000; Malmo Diet and Cancer Cardiovascular Cohort (MDC-CC); Malmo Preventive Project (MPP); and COROGENE.

Analysis revealed that seven of the original 13 variant SNPs were significantly associated with first CHD event.

Meanwhile, for the prospective study, 30,725 participants free from disease at baseline were drawn from FINRISK 1992, 1997, and 2002, Health 2000, and MDC-CC.

After a median follow-up of 10.7 years, 1264 (4%) incident cases of CHD were recorded. Genetic risk score was significantly associated with first CHD event, such that participants in the top quintile of genetic risk score carried a 1.66-fold increased risk for CHD compared with the bottom quintile in a model adjusting for traditional risk factors.

Genetic risk score did not, however, improve C-index over traditional risk factors and family history, nor did it have a significant effect on net reclassification.

Commenting on the study in accompanying article, Manjinder Sandhu and colleagues (University of Cambridge, UK) remained skeptical that genomic risk prediction alone will attain the discriminatory resolution to predict risk for complex diseases at the population level.

"However, the use of genomic factors for individual disease risk prediction in conjunction with conventional risk factors, or for identifying subgroups for screening, remains unclear," they added.

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