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Quantifying direct genetic signal captured by principal component adjustment.

Ramina Sotoudeh^1,2, Sam Trejo^3,4, Arbel Harpak^5,6,7

¹Department of Sociology, Yale University, New Haven, CT 06511.

Proceedings of the National Academy of Sciences of the United States of America

|April 30, 2026

Summary

Principal components (PCs) in genomic studies capture direct genetic effects on complex traits, though these effects are typically small. Adjusting for PCs slightly reduces direct genetic signals but does not significantly impact polygenic index (PGI) estimates.

Keywords:

polygenic indices polygenic scores population stratification population structure sociogenomics

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Area of Science:

Genetics
Bioinformatics
Population Genetics

Background:

Genomic studies of complex traits often adjust for population stratification using principal components (PCs) of the genotype matrix.
The impact of this adjustment on direct genetic effects and polygenic index (PGI) estimates is not fully understood.

Purpose of the Study:

To investigate whether adjusting for PCs in genomic analyses discounts direct genetic effects.
To assess the influence of PC adjustment on PGI estimates within families.

Main Methods:

Utilized family-based models controlling for parental genotype within the UK Biobank dataset.
Analyzed nine complex phenotypes to evaluate the capture of direct genetic effects by PCs.

Main Results:

Principal components (PCs) were found to capture direct genetic effects for all nine tested phenotypes.
These captured direct genetic effects were generally small and comparable to population-level effects.
Adjusting for PCs minimally attenuated direct genetic signals but did not substantially alter PGI estimates within families.

Conclusions:

Direct genetic effects captured by PCs are modest for the studied phenotypes and populations.
PC adjustment in genomic studies slightly diminishes direct genetic signals but has a negligible impact on PGI estimates.