Polygenic risk scores are a critical innovation in evaluating the risks of complex conditions. Sir Peter Donnelly, founder of Genomic PLC) presented on polygenic risk scores and their implications for the future of healthcare in a Thermo Fisher Scientific sponsored discussion. Below is one segment from the talk focusing on the background of polygenic risk scores.
The concept of a polygenic risk score is relatively simple. Complex genetic conditions are usually the result of many contributing genes and mutations, not singular events. Each gene or mutation makes a small contribution to the overall risk, and the chance of developing the condition increases with each additional mutation. Some mutations, in turn, are protective, reducing disease risk. Polygenic risk scores provide a single value that combines the contributions of all gene variants known to contribute toward the risk of a particular disease, giving a sense of the total risk a particular person faces. Some people with low risk scores develop the disease and some with high scores do not, but the population-level pattern provides a way to focus care and resources, particularly those that can protect against the disease, toward people who are most likely to benefit from them.
Polygenic risk scores depend on the accuracy and completeness of the data used to calculate them. This makes bodies of information such as the UK Biobank invaluable. This massive body of genomic data is correlated with medical histories and similar information, providing the ideal data set for connecting genomic variants to disease risks. By studying this data and the medical information being fed into it as its participants continue to live their lives, researchers can evaluate the risks posed by relevant gene variants and discover new ones. This is especially important for identifying and quantifying the impact of variants that make small contributions to the overall risk, or that interact with other variants in unusual ways. More than ever before, data sets like the UK Biobank are helping turn the detailed, sometimes-difficult workings of complex gene networks into information that clinicians and medical systems can use to make direct differences in people’s lives, and work like Sir Donnelly’s is leading the way.