ZMIX: estimating ancestry proportions using GWAS association Z-scores.

Abstract

Motivation: With larger and more diverse studies becoming the standard in genome-wide association studies (GWAS), accurate estimation of ancestral proportions is increasingly important for summary-statistics-based methods such as those for imputing association summary statistics, adjusting allele frequencies (AFs) for ancestry, and prioritizing disease candidate variants or genes. Existing methods for estimating ancestral proportions in GWAS rely on the availability of study reference AFs, which are often inaccessible in current GWAS due to privacy concerns.

Results: In this study, we propose ZMIX (Z-score-based estimation of ethnic MIXing proportions), a novel method for estimating ethnic mixing proportions in GWAS using only association Z-scores, and we compare its performance to existing reference AF-based methods in both real-world and simulated GWAS settings. We found that ZMIX offered comparable results to the reference AF-based methods in simulation and real-world studies. When applied to summary-statistics imputation, all three methods produced high-quality imputations with almost identical results.

Availability and implementation: https://github.com/statsleelab/gauss.