Polygenic risk score (PRS)
Also known as: PRS, polygenic score, genetic risk score
A polygenic risk score (PRS) estimates a person's inherited risk for a common disease, such as heart disease, type 2 diabetes, or breast cancer, by adding up the small effects of thousands or even millions of genetic variants.
Unlike single-gene tests, it captures the combined influence of many genes. While PRS can identify people at substantially higher risk, the scores work less accurately for people of non-European ancestry, and their use in screening embryos is deeply controversial.
Polygenic risk score (PRS), explained at three levels
At home
Think of your height. No single gene decides it; thousands each add or subtract a tiny amount. Many common diseases work the same way. A polygenic risk score adds up the small effects of many genetic variants you carry to estimate whether your inherited risk for a condition, such as heart disease, is lower or higher than average. It nudges the odds; it is not a diagnosis.
At work
A polygenic risk score is a number estimating a person's inherited risk of a common disease, calculated from many genetic variants. Health systems and insurers are interested because it could target prevention, such as earlier screening or cholesterol treatment, at higher-risk people. Its value depends on accuracy in the population being tested and on a clear action tied to each result.
At home
Researchers compare the DNA of hundreds of thousands of people with and without a disease and record which variants appear slightly more often in those who have it, and by how much. Your score multiplies each variant you carry by its weight and adds them up. The total is reported as a percentile. Being in the top 5% might mean two to three times average risk, but lifestyle and environment still shape whether disease develops.
At work
PRS are built from genome-wide association study (GWAS) summary statistics, using methods such as clumping and thresholding or Bayesian approaches like PRS-CS to weight variants and handle correlated ones. Scores are then validated in independent cohorts. Clinically, they add most when combined with existing tools, such as cardiovascular risk calculators or breast cancer models like CanRisk. Guidelines on routine use are still developing, and published scores are catalogued in the PGS Catalog.
At home
PRS weights come mostly from studies of people of European ancestry. Variants that tag disease risk in one population may tag little in another, because the patterns of which variants travel together differ between ancestries. As a result, scores can be several times less accurate for people of African ancestry. While the method itself is sound, in my opinion using PRS in care before fixing that gap risks widening health inequities rather than closing them.
At work
Assess a PRS on validation in cohorts that match your population, discrimination (how well it ranks people), calibration (whether predicted risk matches observed outcomes), and added value over clinical tools. Many scores improve ranking only modestly once age, sex, and family history are included. Communicate results as probabilities. For embryo selection, expected gains are small and uncertain, and bodies such as the European Society of Human Genetics have called the practice unproven and unethical.
Real-world examples
At home
Thomas received a consumer genetics report saying his polygenic risk for heart disease was in the top 10%. His doctor explained it was one risk factor among many, checked his cholesterol, and they agreed on earlier monitoring.
At work
Carlos is a researcher at a Canadian genomics institute. His team is studying whether adding PRS to breast cancer risk models can safely adjust screening ages, while testing accuracy across South Asian, Black, and East Asian participants.
How it compares
| feature | Polygenic risk score (PRS) | Single-gene test |
|---|---|---|
| Genetic basis | Thousands of small-effect variants | One high-impact variant, such as BRCA1 |
| Risk increase | Modest to moderate | Often large |
| Who it applies to | Everyone has a score | Carriers of rare variants |
| Accuracy across ancestries | Varies widely | More consistent |
Single-gene tests find rare big risks. PRS estimates common small ones added together.
For analysts
Polygenic scores are appearing in wellness and insurance discussions. I'd insist on evidence of accuracy for your actual population and a clear clinical action tied to each result before offering or using them.
History & origin
Genome-wide association studies (GWAS), which became practical around 2007, found that common diseases are influenced by many genetic variants, each with a tiny effect. A 2009 schizophrenia study by the International Schizophrenia Consortium showed combining many variants into one score had predictive power. A 2018 Nature Genetics paper by Amit Khera and colleagues reported that PRS could identify people with coronary artery disease risk comparable to rare single-gene mutations, drawing wide attention. Consumer genetic companies and clinical trials began offering scores. Companies selling polygenic embryo screening to IVF patients emerged in the 2020s, prompting criticism from genetics societies. In my view, PRS is a useful risk factor, like cholesterol, not a genetic fortune-telling tool.