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Genetic markers poor at heart disease prediction

8 March 2010
Appeared in BioNews 548

A genetic risk score based on several genetic markers associated with cardiovascular disease (CVD) does not improve the prediction of CVD risk, research published in the Journal of the American Medical Association has suggested. In contrast, the authors found that family history of CVD was a strong predictor of CVD risk.

Nina Paynter and colleagues, from the Brigham and Women's Hospital in Boston, searched the National Human Genome Research Institute catalogue of genome-wide association studies published between 2005 and 2009 to identify genetic markers associated with CVD, and developed two genetic risk scores. The primary genetic risk score included 101 SNPs (single nucleotide polymorphisms) associated with CVD and its intermediate conditions, such as high blood pressure or cholesterol levels. The secondary genetic risk score included 12 SNPs directly associated with incidents of CVD. The authors then tested whether these genetic risk scores were able to predict CVD events, based on data from 19,313 participants in the Women's Genome Health Study, who were followed up during a median period of 12.3 years. Genetic, health and family history information were collected from all participants.

During the follow-up, 777 CVD events occurred in this group of women (199 heart attacks, 203 strokes, 63 cardiovascular deaths, 312 coronary artery revascularisations). When used alone, the genetic risk score was not able to predict CVD risk. After adjustment for age, the genetic risk score was associated with an increased risk of CVD. However, after adjusting for all traditional risk factors (blood pressure, smoking status, diabetes, cholesterol, C-reactive protein, and family history of heart attacks), the genetic risk score was not able to predict CVD risk. The authors concluded that the genetic risk score was not associated with a significant improvement in CVD risk prediction beyond the traditional risk factors.

Many researchers hope that genome-wide association studies - which have identified several genetic markers associated with several common complex diseases including CVD - could be used to improve the prediction of disease risk. This study suggests that in the case of CVD, however, a genetic risk score based on genome-wide association studies does not enhance the accuracy of established prediction methods that do not rely on genetic information.

The authors stressed that their findings do not undermine the importance of genetic studies in understanding disease, but show they are not clinically useful for predicting CVD risk. They wrote: 'While the importance of genetic data in understanding biology and etiology is unchallenged, we did not find evidence in this study of more than 19,000 women to incorporate the current body of known genetic markers into formal clinical tools for cardiovascular risk assessment'.

They suggest that family history may be the strongest predictor of CVD because it 'integrates shared genetics, shared behaviours, and environmental factors'.

The authors also state that 'genome-wide testing is increasingly available and marketed to the general public', and their findings call into question the utility of these tests. 'Our study finds no clinical utility in a multilocus panel of SNPs for cardiovascular risk based on the best available literature'.

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