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Polygenic risk · 7 min read

A polygenic score is only as good as its ancestry

A score that means average in one population can mean high in another.

Polygenic risk scores (PRS) summarise the combined effect of thousands of variants into a single number. They are one of the most promising tools in preventive genomics — and one of the easiest to get dangerously wrong.

The portability problem

Most PRS were derived from genome-wide association studies in predominantly European-ancestry cohorts. Applied to a person of a different ancestry, the same raw score can land at a completely different percentile of true risk. A score that means “average” in one population can mean “high” in another. Reporting it without calibration is not just imprecise — it is misleading.

A polygenic score without an ancestry is a number without units. It looks quantitative, but you cannot safely say what it means.

Calibrating explicitly

Innovare computes polygenic scores against reference panels and infers ancestry explicitly using an approach (PCA against reference panels). The inferred ancestry then drives calibration, so a percentile means the same thing regardless of background — with particular attention to the Iberian and admixed Latino populations our clients serve, which are underrepresented in most published scores.

Reproducible, layered, reviewable

Every score is traceable: the reference used, the ancestry inferred, the calibration applied. Coverage gates decide whether a score is reportable at all. The goal is a PRS a laboratory can stand behind — not a black-box number that happens to look precise.

Scope. Our published work on this module is an analytical validation of the computation — harmonisation, weighted summation, absent-site handling and interpretation logic — not evidence of predictive validity. Establishing clinical validity requires phenotyped cohorts and is not something a software vendor can do alone.

See it run on your data

Request a demo of the full chain — from raw reads to a reviewable, signable report.

app.innovaregenetics.com · for clinical & research laboratories