Scientists bring polygenic risk scores closer to clinical use

Institute news

Researchers have established the first universal reporting standards and open access platform for polygenic risk scores, paving the way for widespread clinical use of genetic testing to better determine an individual’s risk of various common diseases.

Over the past decade, researchers have worked to expand the use of genetic data in the clinic. This includes a powerful method to calculate an individual's inherited risk for various diseases, such as coronary heart disease, type 2 diabetes and stroke. The method, called a polygenic risk score, is generated by measuring DNA variants in more than six million locations across the human genome. 

With the rise in popularity of studies using polygenic risk scores, there have been large variations in how these scores are calculated and reported. There is widespread concern that varied reporting and transparency of polygenic risk scores could hinder clinicians in assessing how well they predict disease risk and how they may be able to help their patients.

To address this issue, two international research teams — both including scientists from the Baker Heart and Diabetes Institute — have today published the 'Polygenic risk score reporting statement' in the journal Nature. This framework defines in detail the information scientists should include in their studies to improve the validity, transparency and reproducibility of polygenic risk scores.

And in the journal Nature Genetics, researchers today launched the first open resource for polygenic scores — the PGS Catalog. This catalogue makes information for each polygenic score publicly available, along with consistent metadata, so scores can be tested and translated for clinical use.

Across both projects, genomics experts at the Baker Institute have closely collaborated with the US National Institutes of Health, Stanford University, EMBL’s European Bioinformatics Institute, University of Cambridge and Health Data Research UK.

In the past decade, researchers have produced more than 900 studies of polygenic scores.

The Baker Institute’s Munz Chair of Cardiovascular Prediction and Prevention Professor Michael Inouye said there needed to be more independent evaluation of which scores offered the best performance and how this varied when important factors changed, such as an individual’s ancestry.

"If researchers can follow the guidelines in the Polygenic risk score reporting statement and pair that with the PGS Catalog it will substantially improve the evaluation of polygenic scores and the determination of which score or scores are best in which clinical settings," he said.

"For cardiovascular diseases and many others, we will be able to confidently place patients in different risk categories and provide beneficial screening strategies and treatments. Ideally, in the future, we will measure genomic risk of disease early enough to combat them more effectively."

This work builds on seminal research by the Baker Institute to develop and validate polygenic risk scores to help predict and prevent disease.

A polygenic risk score developed by the Institute to predict a person’s risk of coronary artery disease will be tested in 1000 people this year, as part of the EDCAD-PMS study in Melbourne.