Equip DNA Info Lab · Revisió editorial · 20 de maig del 2026 · 7 min de lectura

Polygenic risk scores (PRS) for non-scientists

Almost every modern genetics report talks about polygenic risk scores, or PRS. The term sounds intimidating but the underlying idea is straightforward. Here's the plain-English version, plus what a PRS can and can't tell you about your health.

One gene, many genes

Some conditions are caused by a single gene. Cystic fibrosis, sickle cell anaemia, Huntington's disease — these are "monogenic" diseases where one mutation deterministically causes the condition. Genetics there is binary: you have the variant or you don't.

Most common conditions are different. Type 2 diabetes, heart disease, depression, obesity, most cancers — these are polygenic. Hundreds or thousands of genetic variants each contribute a tiny bit to your overall risk. No single one is decisive. The total is what matters.

What a PRS actually computes

A polygenic risk score adds up the contributions of all known risk variants for a given condition, weighted by how strong each one is. Conceptually:

PRS = Σ (your dose of variant i × effect size of variant i)

"Dose" is 0, 1 or 2 — how many copies of the risk allele you carry at that position (you have two copies of each chromosome, so the maximum is 2). "Effect size" comes from genome-wide association studies (GWAS) — peer-reviewed papers that measured how much that variant moved disease risk in thousands of people.

How to read your score

Raw PRS numbers are not meaningful on their own. They become meaningful when compared against a population distribution — your score's percentile. A percentile of 80, for example, means your genetic loading for that condition is higher than 80% of people in the reference population.

Most reports classify scores into three tiers — ours does not, and the section below explains why:

• Low — below the 50th percentile of the reference population.
• Moderate — between the 50th and 80th.
• High — above the 80th.

A "high" PRS is not a diagnosis, and there is no general conversion from a percentile to a lifetime risk. What a high score means in absolute terms depends on the disease, on the particular score, on the reference population it was calibrated in and on how common the condition is to begin with; the NHGRI makes the point that two people with the same score can carry different lifetime risks, and that a score on its own supplies neither a baseline nor a time horizon. Only a score validated for one disease in one population can be turned into a risk figure at all. Lifestyle, environment, and other genes you didn't inherit also matter, often more than the polygenic component.

The limitations

There are four big caveats to keep in mind:

1. Ancestry bias. ~90% of all GWAS participants are of European descent. PRSs trained on European data underperform — sometimes drastically — on African, East Asian, South Asian and Hispanic/Latino populations.
2. Chip coverage. Microarray-based tests (23andMe, AncestryDNA, MyHeritage) only measure ~0.02% of the genome. Most GWAS variants are covered, but some PRS calculations would benefit from whole-genome sequencing.
3. Effect size uncertainty. Each effect size is itself an estimate with a confidence interval. Aggregating many small effects amplifies noise as much as signal. A "high" PRS from one provider and "high" from another may come from different variant lists.
4. Population vs individual. Even a perfectly calibrated PRS tells you about the average risk of people like you, not your personal outcome. Two people with identical scores can have radically different lives.

What it's actually useful for

With those caveats, a PRS is a starting point for a conversation, not a verdict. For some conditions — coronary artery disease, type 2 diabetes, breast cancer — a high PRS is now considered actionable enough by some clinicians to motivate earlier or more aggressive screening. For most conditions, it's information you can use to inform lifestyle choices: high cardiovascular PRS → take blood pressure more seriously; high lipid PRS → get a fasting lipid panel earlier.

Crucially: a low PRS does not protect you. Smokers with low cardiovascular PRS still get heart disease.

What our reports show instead

Our own audit found that most of a category's combined effect came from studies measuring something other than the condition it names — so we withdrew the aggregate number rather than publish one we cannot defend. What a report shows today is every variant of yours that matches the GWAS Catalog (genome-wide significance, p < 5×10⁻⁸), with the trait its study actually measured, the published effect (OR or beta) and a link to the source, plus a plain-language explanation. No aggregate score, no band, no percentile. The methodology page has the full details.

Aquest article té finalitats exclusivament educatives i no constitueix consell mèdic, diagnòstic ni tractament. Consulta sempre un professional sanitari per a decisions sobre la teva salut.