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September 10, 2025Open Access

Within-family validation of polygenic risk scores in the UK Biobank: Investigating the role of principal component analysis and mixed model association

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Authors

CKCiaran Michael KellyOOOnyedika OnuorahEGEdmund Gilbert

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Overview

Observational analysis reveals effects of population stratification on polygenic risk scores, suggesting variability across complex diseases.

Key Points

  • Within-family analysis found that increasing the number of principal components does not consistently reduce prediction attenuation.
  • The study examined four complex diseases in the UK Biobank, including coronary artery disease and type 2 diabetes, revealing trait-specific confounding effects.
  • Using mixed model-based approaches showed little added benefit to predictive performance or attenuation reduction.
  • Results highlight the complexity of controlling for population stratification in genetic studies, indicating the need for best practice guidelines.

Cite This Study

Kelly et al. (2025) studied this question.

synapsesocial.com/papers/68c23a74b210217d6478101ehttps://doi.org/10.1101/2025.08.28.25334633
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Also Consider

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