Limited usefulness of genetic risk scores in disease prediction

Polygenic risk scores, used to estimate an individual’s genetic risk for common diseases, including heart disease, need to catch up in their predictive capabilities, as highlighted by a recent study led by UCL researchers

Previously hailed as a potential game-changer in disease prediction and prevention, polygenic risk scores have led to the establishment of companies offering genetic testing services.

Genetic risk scores: A disappointing predictor of common diseases

These scores are also a focus of the nationwide Our Future Health project.

Published in BMJ Medicine, the study assessed 926 polygenic risk scores for 310 diseases, revealing that, on average, only 11% of individuals who eventually developed a disease were correctly identified, with a 5% false positive rate. This means that wrong optimistic predictions often outnumber true positives.

Lead author Professor Aroon Hingorani (UCL Institute of Cardiovascular Science) expressed disappointment in polygenic risk scores’ performance, stating that their medical potential had been overstated. When evaluated against established medical test standards, these scores fell short in predicting and screening for common diseases.

Examining polygenic risk scores

The researchers also examined how polygenic risk scores would perform when combined with conventional screening methods. Thousands of individuals sometimes need genetic testing to prevent just one additional heart attack or stroke, making age-based prescriptions more straightforward and effective.

Need for regulating commercial genetic tests

The study emphasises the need for regulating commercial genetic tests based on polygenic risk scores to prevent unrealistic expectations and undue strain on public health systems. Consumers should be informed of detection rates, false favourable rates, and disease risks associated with these scores to make informed decisions.

Polygenic risk scores: An unfulfilled promise

Polygenic risk scores, distinct from genetic testing for single gene mutations, remain limited in their ability to contribute to public health screening programs. However, identifying variants associated with disease risk remains crucial for drug development, as these variants encode proteins that can be targeted by medications helpful for everyone.

Funding from the British Heart Foundation

The study received funding from the British Heart Foundation, UK Research and Innovation (UKRI), the National Institute for Health and Care Research (NIHR), and the NIHR Biomedical Research Centre at UCLH and UCL.