# Dissecting the Predictive Accuracy of Polygenic Indexes for Behavioral Phenotypes Across Genetic Ancestries

## TL;DR

Polygenic indexes lose accuracy when applied to non-European ancestries, especially for behavioral traits, with different factors causing this loss depending on ancestry.

## Contribution

The study systematically analyzes PGI portability across ancestries for behavioral and health-related traits and compares standard and family-based GWAS-based PGIs.

## Key findings

- PGI predictive power drops significantly for non-European ancestries, with African ancestry showing the largest loss.
- Biologically proximal traits show better portability than behavioral and social traits.
- Family-based GWAS PGIs modestly improve portability for some traits like BMI in African ancestry.

## Abstract

Polygenic indexes (PGIs) trained on samples of European genetic ancestries often lose substantial predictive power when applied to non-European ancestries. While this portability problem is well recognized, its manifestation in behavioral and social traits remains understudied, and the factors driving this accuracy loss warrant more comprehensive analysis. Using data from the UK Biobank and Health and Retirement Study, we conduct a systematic analysis of PGI portability for 52 health-related, behavioral, and social phenotypes. We advance prior literature by using genome-wide PGIs, assessing cross-ancestry heritability differences, and comparing the performance of PGIs based on standard versus family-based GWAS. Our findings confirm systematic reductions in PGI predictive power for non-European ancestries—lowest in African (24%), followed by East Asian (37%) and South Asian (51%) genetic ancestries—with biologically proximal traits exhibiting greater portability than behavioral and social traits. We show that the relative importance of factors underlying reduced portability varies across traits and ancestries: in African ancestries, linkage disequilibrium and allele frequency differences explain most of the loss (82%), compared with smaller contributions in East (34%) and South Asian (25%) ancestries. Finally, we find that family-based GWAS PGIs can modestly improve portability for select traits, such as BMI in African ancestry, suggesting that part of the portability gap may reflect population-specific confounds in standard PGIs.