It has long been known that genetics is a major risk factor for all the common chronic human diseases, such as heart disease, diabetes, osteoporosis, and the mental health and auto-immune disorders, and for the common cancers, such as breast, prostate, and bowel cancer. For many of these diseases, or in some cases for important subsets of individuals, it is the single most important predictor of disease risk. We now know, from 20 years of human genetics studies, that this risk is polygenic: for any given disease, it is due to the cumulative effects of a very large number of different genetic variants in our DNA, each of individually small impact. Polygenic risk scores (PRSs) provide a single measure which quantifies the overall impact of these variants. For many diseases the underlying genetic studies are now large enough to provide good information about which variants matter for a particular disease, and their effect sizes, and in parallel we now have large prospective population cohorts, such as UK Biobank, in which to assess and validate predictive power.

The talk will describe our work in Genomics plc on PRSs and their use, typically in combination with non-genetic risk factors, to provide a new level of risk prediction for common diseases, and the path to their adoption in healthcare systems to empower a new generation of risk-stratified, personalised, disease prevention. The identification of individuals at increased risk of disease who are currently invisible to health systems will allow those systems to get more of the right individuals into the appropriate screening, prevention, and treatment pathways. For the individual, this can help to prevent disease entirely or to catch it early, when outcomes are much better; for the health system, it means existing prevention and screening resources are used more efficiently by deploying them on higher-risk individuals; and from a population health point of view, by moving healthcare towards prevention, lives and resources are saved over time.