Polygenic Risk Scores (PRS) are no longer an exclusively research tool—they are becoming a real complement to clinical diagnosis. In 2025, several European and American clinical guidelines have begun to incorporate PRS into their screening recommendations. What has changed?
What Is a PRS?
A PRS aggregates the effect of thousands or millions of genetic variants, each with a small individual effect, to estimate a person’s relative risk for a given disease. Unlike monogenic variants (such as BRCA1 in breast cancer), a PRS does not determine whether you will develop a disease: it estimates a probability.
From Research to Clinical Practice: What Changed in 2025
Cardiovascular Disease
Since 2024, the European Society of Cardiology has included cardiovascular PRS as a complementary risk factor when evaluating intermediate-risk patients (SCORE2). In patients with a PRS above the 90th percentile, the estimated cardiovascular risk is reclassified upward, which may justify initiating statin therapy.
Breast Cancer
The PERSPECTIVE I&I study (published in JAMA Oncology, 2024) demonstrated that a PRS combined with clinical factors and mammographic density predicts breast cancer risk more accurately than classical models (Tyrer-Cuzick, Gail). Several breast units in Spain are beginning to pilot this approach.
Type 2 Diabetes
UK Biobank studies show that a type 2 diabetes PRS above the 95th percentile confers a risk equivalent to having a diabetic parent. Combined with HbA1c and age, it improves 10-year prediction.
Limitations You Should Be Aware Of
- Population bias: most GWAS have been conducted in European populations. Transferability to other populations is limited, though improving with studies such as All of Us and H3Africa.
- Environmental context: PRS do not capture environmental factors (diet, exercise, smoking) that modulate actual risk.
- Variability across models: not all PRS for the same disease use the same variants or the same weights. Model selection matters.
How We Do It at OmicaLabs
Our PRS pipeline uses PLINK2 on whole genome sequencing data (not imputed from a SNP chip), with validated models from the PGS Catalog and normalisation against a reference panel of 2,500 genomes from the 1000 Genomes Project. Each score is presented with its population percentile and an interpretation in plain language for both the patient and the clinician.
We currently calculate PRS for over 20 conditions, including cardiovascular disease, type 2 diabetes, breast cancer, Alzheimer’s disease, Parkinson’s disease, atrial fibrillation, colorectal cancer, and asthma, among others.
Want to see how a PRS is presented in an actual report? View our sample reports.