Imagine a recipe that’s 99% the same for everyone, but the last 1% changes the flavor completely. That’s your DNA. Humans share about 99% of their DNA, which means we’re more alike than different. However, that remaining 1% can influence factors such as your risk for certain diseases, a topic that researchers at the University of Colorado Anschutz (CU Anschutz) Department of Biomedical Informatics are studying to better understand and predict health outcomes.
Some conditions, like heart disease or diabetes, aren’t caused by a single gene. Instead, they’re influenced by hundreds or even thousands of small genetic differences scattered across your genome. Each variation might only nudge your risk a little, but together, they can add up.
That’s where a polygenic risk score (PRS) comes in. Think of it like packing for a trip:
The heavier the suitcase, the higher your genetic predisposition for that condition. It doesn’t guarantee you’ll get the disease, but it shows how your risk compares to the average person.
As Maggie Stanislawski, PhD, assistant professor of biomedical informatics, puts it, “A polygenic score sums the effects of many individual variants into a single number, providing insights into the likelihood of developing a particular disease.”
Most of the time, your health isn’t determined by a single gene—it's the combined effect of many. But sometimes, one small change in your DNA can have a huge impact. That is what scientists call a monogenic mutation.
Think of your genome as a massive instruction manual for building and running your body. A monogenic disease happens when one single letter in that manual is incorrect in a critical location. That typo can completely change the meaning of the sentence. In genetics, that “letter” is a nucleotide, and when it’s altered in the wrong place, it can disrupt how a protein works.
A classic example is sickle cell anemia. Here, a single nucleotide mutation changes the structure of hemoglobin—the protein that carries oxygen in your blood. That tiny tweak makes red blood cells stiff and crescent-shaped instead of soft and round. These misshapen cells can clog blood vessels, reduce oxygen delivery and cause painful complications. All from one genetic typo.
Monogenic diseases are rare but powerful because they often have a direct cause-and-effect relationship: one mutation, one disease. Compare that to complex conditions like diabetes or heart disease, which involve hundreds or thousands of genetic factors plus lifestyle and environment.
Most diseases are polygenic. That’s why PRS is exciting: it helps researchers estimate risk for complex conditions and could one day guide personalized prevention and treatment.
Imagine knowing your risk for heart disease decades before symptoms appear and getting tailored advice to lower that risk. That’s the potential of PRS.
But there are challenges. Current scores mostly use data from people of European ancestry, which limits accuracy for other populations. Additionally, PRS only looks at genetics. It does not yet factor in lifestyle, environment or other health data.
Joanne Cole, PhD, assistant professor of biomedical informatics, cautions, “For these scores to serve as a reliable tool in personalized medicine, they must integrate with a person’s broader health profile.”
Researchers are working to make PRS more inclusive and integrated. If they succeed, these scores could become a powerful tool for predicting disease risk early and tailoring care to each individual.