Crunching Numbers in Your Genes
How Polygenic Risk Scores Shape Your Health Forecast
Nov 14, 2023Do you ever wonder why some people might be more likely to get certain diseases?
Scientists wonder as well, and they’ve developed something called a "polygenic risk score" to help understand why. In many ways, your personal traits, like height and eye color, are made up of tiny instructions in your DNA called genes. Polygenic risk scores use thousands of these genes to predict if a person might have a higher chance of getting a specific illness, like heart disease. Adding up the varying effects of many genes related to a disease allows scientists to create a score. If the score is high, it means there's a greater chance of getting sick. Polygenic risk scores help doctors learn about who might need extra care and what we can do to stay healthy. Researchers have developed a central database of score units—the genes used to calculate different polygenic risk scores—called the Polygenic Score Catalog. It allows scientists to use, test and share scores worldwide.
Researchers at the Colorado Center for Personalized Medicine recently combined genetic data with data from health records to study how well 3,000 polygenic risk scores from the Polygenic Score Catalog predict disease in a population of more than 73,000 biobank participants.
What did they find?
For approximately 100 diseases, researchers found that biobank participants with polygenic risk scores in the top 10% were at more than double the risk for developing that specific disease. This included some common conditions like type 2 diabetes and high blood pressure. Even after accounting for differences in a participant’s age, sex and genetic ancestry, some of these risk predictions remained present and strong.
Some polygenic risk scores do not work for everyone. They can be better at predicting certain health traits for some ancestry groups than for others or have different scales of predicted risk among ancestry groups. Researchers are working to understand why this happens. If one score works for everyone, it will be easier for health care providers to use the score when treating patients. However, accounting for these differences in predicted effects may also be a good way to personalize healthcare. After all, we are all different and unique.
Often, certain diseases are genetically linked with others. For example, diabetes is known to cause chronic kidney disease. Not all polygenic risk scores in the Catalog are developed enough to tease out these links. So researchers caution health care decision-makers to understand how each score is developed. If a polygenic risk score is not well-developed or does not work well in certain ancestry groups, these related causal associations might be missed in clinical care.
This polygenic risk score research will be showcased at an upcoming national human genetics conference. CU Anschutz is fortunate to have a core group of researchers interested in how we can predict genetic risk, particularly across diverse populations. Their research assists us in improving diagnosis precision around genetic differences in diseases. Especially to distinguish between similar illnesses (for example, type 1 diabetes in adulthood vs. type 2 diabetes) so people can receive the correct treatment as early as possible. While exciting work has been done, we’ve found that there remain many challenges in using polygenic risk scores to benefit different groups of people. Your participation in the biobank helps us work toward overcoming these obstacles and personalize and transform health care in the future.
