Genetic risk scores not useful in predicting disease

 Polygenic risk scores, which estimate a person's disease risk based on thousands or millions of common genetic variants, perform poorly in screening and prediction of common diseases such as heart disease, according to a new study led by UCL (University College London) researchers.

It has been claimed that polygenic risk scores will transform the prediction and prevention of common diseases. Companies have already been established that sell polygenic risk score testing services. Polygenic risk score testing is also one of the aims of the nationwide Our Future Health project.

The new study, published in BMJ Medicine, looked at 926 polygenic risk scores for 310 diseases. It found that, on average, only 11% of individuals who develop disease are identified, while at the same time 5% of people who do not develop the disease test positive. Unaffected people usually outnumber those affected which results in far more false than true positive predictions.

Lead author Professor Aroon Hingorani (UCL Institute of Cardiovascular Science) said: "Strong claims have been made about the potential of polygenic risk scores in medicine, but our study shows that this is not justified.

"We found that, when held to the same standards as employed for other tests in medicine, polygenic risk scores performed poorly for prediction and screening across a range of common diseases."

For the new study, researchers looked at data available in an open-access database, the Polygenic Score Catalog, to determine what the detection rate and false positive rate of the scores would be if used in screening.

For breast cancer and coronary artery disease, the risk scores identified only 10% and 12% of eventual cases respectively, using a cut-off that resulted in 5% of unaffected individuals testing positive.