Within-sibling attenuation of polygenic risk score accuracy: investigating the effects of principal component analysis, LD score regression, and mixed model association in the UK Biobank.

Abstract excerpt

A central challenge in polygenic risk prediction is measuring and controlling for confounding due to population stratification. Standard approaches include adjusting for leading principal components (PCs) of genetic variation and using linear mixed models in genome-wide association studies (GWAS). Evidence of adequate control is typically inferred from reductions in the linkage disequilibrium score regression...

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