Within-family validation of a new polygenic predictor of general cognitive ability

We present a polygenic score (PGS) for general cognitive ability (GCA) that demonstrates a substantial increase in predictive accuracy both among unrelated individuals and within-families relative to existing predictors. In the UK Biobank (UKB), our PGS achieves a standardized regression coefficient with fluid intelligence of β=0.406 (SE 0.009), corresponding to an R² of 16.4% (95% confidence interval: [15.1%, 17.9%]). In a sample of 4,642 sibling pairs from UKB, we estimate the standardized within-family effect of the PGS to be δ=0.355 (SE 0.0218), indicating only slight attenuation of prediction ability within-family (δ/β=0.876, SE 0.050). We obtain similar results in a sample of 736 9-10-year-old European ancestry sibling pairs from the Adolescent Brain Cognitive Development (ABCD) cohort. After correcting for the reliability of the UK Biobank and ABCD phenotypes, the inverse-variance-weighted within-family association of the PGS with latent general ability is estimated at 0.448 (SE 0.025). Our PGS predicts higher educational attainment, occupational status, and family income within families, and retains good performance in non-European ancestry samples, with the correlation retaining 64% of its magnitude in the African American subset of the ABCD cohort, in line with expectations. In UKB siblings, higher scores correlate with better self‑reported health and lower risk of multiple cardiometabolic diseases. Our study shows that it is possible to attain powerful within-family prediction of GCA using a PGS, enabling future research to clarify how cognitive ability influences health-related outcomes.