Polygenic scores perform poorly in predicting common diseases

Polygenic risk scores perform poorly if used to predict common diseases such as coronary artery disease or breast cancer, a University College London (UCL) study has found.

The researchers analysed open-access data publicly available from the Polygenic Score Catalogue in an attempt to elucidate risk score performance in screening for common diseases – specifically in population screening, individual risk, and population risk stratification.

Professor Aroon Hingorani from UCL Institute of Cardiovascular Science, who led the research, explained: '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.'

The study, published in BMJ, analysed 926 polygenic risk scores for 310 diseases. It focused on coronary artery disease and breast cancer as examples, demonstrating that the risk scores predicted just 12 percent and ten percent of future cases, respectively. Furthermore, 89 percent of individuals had a false negative result, while five percent had a false positive result.

'It has been suggested that polygenic risk scores could be introduced early on to help prevent breast cancer and heart disease but, in the examples we looked at, we found that the scores contributed little, if any, health benefit while adding cost and complexity,' said Professor Sir Nicholas Wald, a co-author of the study from UCL Institute of Health Informatics. 'Our results build on evidence that indicates that polygenic risk scores do not have a role in public health screening programmes.'

Polygenic risk score testing is among the aims of the UK-wide Our Future Health programme – a collaboration between the public, charity and private sectors to develop new ways to prevent, detect and treat disease (see BioNews 1165). Dr Raghib Ali, the chief medical officer of Our Future Health, who was not involved in the UCL study, told the Guardian that Our Future Health aims to integrate the polygenic scores with other risk measures such as deprivation, lifestyles and environment. He emphasised that due to the novelty of this approach, many unknowns still remain.

The researchers also urge caution with regard to availability and usefulness of commercial genetic tests based on polygenic risk scores, to 'protect the public from unrealistic expectations and already stretched public health systems from becoming overburdened by the management of false positive results'. In fact, they propose stricter regulation for these commercial products.

James Ware, professor of cardiovascular and genomic medicine at Imperial College London, who was not involved in the study said: 'The authors do a very good job of highlighting the limitations of applying polygenic risk scores in a population screening context, and laying out some of the concerns around potential clinical implementation.... The authors acknowledge that [polygenic risk scores] can improve the accuracy of conventional risk scores used today... but they highlight that the improvement is modest: you would need to genotype thousands of individuals to prevent a significant cardiovascular event. You could prevent the same number of events more simply and cheaply by lowering the threshold for prescribing a statin.'