| Title: | Interpreting Polygenic Prediction of Cognitive Ability: Evidence for Direct, Reliable, and Portable Genetic Effects |
| Journal: | - |
| Published: | 6 Apr 2026 |
| DOI: | https://doi.org/10.65550/001c.158459 |
Publication 18089
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Abstract
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 δ / β ≈ 0.88 ). 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. </p>
6 Authors
- Tobias Wolfram
- Spencer Moore
- Jeremiah H. Li
- Jonathan Anomaly
- Ivan Davidson
- Michael Christensen
1 Application
| Application ID | Title |
|---|---|
| 103244 | Comprehensive evaluation of direct contributions of rare and common variants to genetic risk prediction |
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