Polygenic risk score (PRS)

A polygenic risk score (PRS) sums up your genetic risk for a trait across many small DNA variants (SNPs). Each variant gets a weight, usually drawn from big genome-wide studies (GWAS), using methods like P+T or Bayesian shrinkage (LDpred, PRSice). For common complex diseases (coronary artery disease, type 2 diabetes, breast cancer), a high PRS can flag people whose lifetime risk rivals that of single-gene mutation carriers. That hints at real value for targeted prevention. But there is a major catch. PRS works much worse across ancestries, because the discovery GWAS were mostly European, and DNA patterns and variant frequencies differ between populations. That limits fair, equitable use. Other challenges: the scores can drift out of calibration over time, they miss rare variants and gene-environment interactions, and it is unclear whether a PRS for longevity is even a useful clinical endpoint, given how composite and late-acting it is.

Last reviewed: June 22, 2026

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