What is a Polygenic Risk Score (PRS)?

Most common diseases - heart disease, type 2 diabetes, many cancers - aren’t caused by a single faulty gene. They arise from the combined effect of hundreds or thousands of small DNA differences scattered across your genome, each nudging your risk up or down by a tiny amount. A polygenic risk score (PRS) adds up these small effects to estimate your inherited risk for a particular condition.

Unlike a diagnostic gene test that looks for one rare, high-impact mutation (such as BRCA1 for breast cancer), a PRS reads large numbers of common genetic variants - typically hundreds to millions - that each contribute a little to disease risk. The score tells you where you sit on a spectrum: higher than average, average, or lower than average inherited risk compared with other people of similar ancestry.

How does a polygenic risk score work?

A PRS is calculated in three steps:

1. Genome-wide genotyping. A laboratory reads hundreds of thousands (or millions) of positions in your DNA where people commonly differ - these positions are called single nucleotide polymorphisms, or SNPs (pronounced “snips”). Each SNP is like a letter in the genome that can vary: for example, some people have an A at a particular spot, others have a G.

2. Weighting the variants. Scientists have performed large studies comparing the genomes of people who developed a disease (cases) with those who didn’t (controls). From these studies, researchers know which SNPs are more common in people with the disease, and by how much. Each SNP gets a weight - a number reflecting how strongly it’s associated with the condition.

3. Summing your score. The lab looks at which version of each SNP you carry, multiplies by the weight, and adds up all the contributions. The result is your polygenic risk score - a single number. The lab then compares your score with a reference population (people of similar ancestry) and tells you what percentile you’re in. A score in the 90th percentile means your inherited risk is higher than 90% of the reference group; a score in the 30th percentile means it’s lower than 70% of the group.

The score reflects only the genetic component of risk. It doesn’t account for lifestyle, environment, or other non-inherited factors.

What can a polygenic risk score tell you?

A PRS can estimate your relative inherited risk for conditions where many genes play a role. These include:

• Cancers: breast, ovarian, prostate, colorectal, pancreatic, melanoma
• Heart and circulatory diseases: coronary artery disease, stroke, atrial fibrillation
• Metabolic conditions: type 2 diabetes, high cholesterol (high LDL, low HDL), obesity
• Neurological conditions: Alzheimer’s disease, Parkinson’s disease
• Autoimmune and inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease, asthma

How much a PRS separates higher- from lower-risk people varies a lot by condition. Coronary artery disease has one of the strongest scores: in a large study, around 8% of people fell in a top group with more than three times the average risk. For most other conditions the spread is smaller - for breast cancer, for example, the same study found only about 1.5% of people reached that same threefold threshold. Estimates also depend on how the high-risk group is defined and on a person’s ancestry.

A high PRS doesn’t mean you will get the disease, and a low PRS doesn’t mean you won’t. The score is one piece of information. Your doctor will consider it alongside your family history, lifestyle, and clinical risk factors (blood pressure, cholesterol, smoking, weight) to decide whether earlier or more frequent screening, or preventive treatments, make sense for you.

What a polygenic risk score cannot do

It’s important to understand the limits:

• It’s not a diagnosis. A PRS estimates inherited risk, not whether you currently have a condition. If you have symptoms, you need clinical tests - not a genetic score.

• It doesn’t replace standard screening. Everyone should follow NHS screening guidelines (cervical screening, bowel cancer screening, breast screening). A PRS may help decide whether to start earlier or screen more often, but it doesn’t replace the screening itself.

• It doesn’t detect rare high-risk mutations. A PRS won’t find pathogenic variants in genes like BRCA1, BRCA2, or Lynch syndrome genes. If you have a strong family history suggesting a hereditary cancer syndrome, you need a different kind of test (a diagnostic gene panel), not a polygenic score.

• Accuracy varies by ancestry. Most of the large genetic studies used to build PRS models have been done in people of European ancestry. Scores are less accurate - sometimes much less accurate - for people of African, East Asian, South Asian, or mixed ancestry. Labs are working to improve this, but it remains a significant limitation. Your genetic counselling session should explain how much confidence to place in your score given your ancestry.

• Predictive power varies by condition. Some scores (coronary artery disease, breast cancer) explain a meaningful chunk of inherited risk. Others (type 2 diabetes, Alzheimer’s) explain less, because environmental factors or rare variants not captured by the PRS play a bigger role. Again, counselling helps you interpret what the number means in practice.

How might you use a polygenic risk score?

A PRS is most useful when combined with other information. Examples:

• Breast cancer screening. A woman with a high polygenic risk score for breast cancer and a moderate family history might benefit from starting mammograms at age 40 instead of 50, or adding MRI screening. Her GP or a breast clinic can advise.

• Heart disease prevention. A man with a high coronary artery disease PRS and borderline-high cholesterol might be offered a statin earlier than guidelines would otherwise suggest, because his genetic risk tips the balance.

• Tailoring lifestyle advice. Someone with a high type 2 diabetes PRS might be especially motivated to maintain a healthy weight and stay active, knowing they have a higher inherited susceptibility.

• Family planning. In some cases, knowing your polygenic risk for a condition that runs in families can inform reproductive decisions, though PRS is less deterministic than single-gene tests.

The key is that a PRS provides additional context for decisions you and your doctor are already making. It doesn’t dictate a single course of action.

Who offers polygenic risk score testing?

PRS testing is not yet part of routine NHS care for most people. The NHS Genomic Medicine Service uses PRS in a few specialist settings (for example, stratifying breast cancer risk in women with a family history), but widespread rollout has not happened.

Commercial labs, including Jeen Health, offer PRS testing privately. The test typically involves a saliva or cheek-swab sample you collect at home. The lab analyses your DNA, calculates scores for multiple conditions, and provides a report. Reputable services include genetic counselling to help you interpret the results.

What you can do at Jeen

Jeen’s Polygenic Risk Score Test provides ancestry-specific risk estimates across more than 20 conditions - including common cancers (breast, ovarian, prostate, colorectal, pancreatic, melanoma), heart disease and stroke, cholesterol and lipid disorders, type 2 diabetes, and Alzheimer’s disease. The test uses a simple at-home saliva kit (no clinic visit, no blood draw) and is powered by Allelica’s ancestry-adjusted models, which account for differences in genetic architecture across populations.

Your report includes polygenic risk scores for each condition, showing where you sit relative to others of similar ancestry. The test estimates inherited risk only - it’s not a diagnosis, not a definitive prediction, and not a replacement for NHS screening programmes. Predictive performance varies by condition and by ancestry, and your genetic-counselling consultation (included with every test) explains how much weight to give each score in your particular situation.

The counselling session is especially important if your ancestry is under-represented in genetic research, if you have existing risk factors or a family history, or if you’re considering changes to screening or prevention based on your results. Your counsellor will help you integrate your polygenic risk scores with your clinical picture and guide next steps, including when to involve your GP.