Interpreting Polygenic Prediction of Cognitive Ability: Evidence for Direct, Reliable, and Portable Genetic Effects

The interpretation of polygenic scores (PGS) for general cognitive ability (GCA) remains contested, with concerns about indirect genetic effects, environmental confounding, cross-ancestry portability, and the gap between PGS prediction and twin heritability estimates. Relying on a newly constructed PGS using within-family designs in two independent sibling cohorts (UK Biobank, N=4,642 pairs; ABCD, N=736 pairs), we demonstrate that direct genetic effects account for the large majority of PGS prediction (within-family attenuation <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"> <mml:mrow> <mml:mi>δ</mml:mi> <mml:mi>/</mml:mi> <mml:mi>β</mml:mi> <mml:mo>≈</mml:mo> <mml:mn>0.88</mml:mn> </mml:mrow> </mml:math> ). Correcting for measurement error in brief cognitive assessments, the within-family association with latent general ability is approximately 0.45, substantially higher than observed-scale estimates. Cross-ancestry portability follows theoretical expectations (66% effect retention in African Americans). Within families, higher PGS predicts greater educational attainment, occupational status, and reduced cardiometabolic disease risk, with no evidence for gene-environment interactions or substantial adverse pleiotropy. These findings replicate using a benchmark predictor based on publicly available data, confirming they reflect properties of cognitive genetic architecture rather than idiosyncrasies of a particular score.