# A reanalysis of a genome-wide association study on breast cancer in Asian populations using the SG10K_Health reference panel for imputation: a multi-Centre case–control analysis

## TL;DR

This study shows that using a population-specific reference panel improves the detection of genetic variants linked to breast cancer in Asian populations.

## Contribution

The study demonstrates the importance of using an Asian-specific imputation panel for more accurate variant discovery in breast cancer GWAS.

## Key findings

- SG10K_Health imputed more rare variants and achieved higher accuracy for rare alleles in Asian populations.
- The 1000 Genomes panel performed better for common variants in some contexts.
- Panel choice influenced association signals at breast cancer loci like FGFR2, TOX3, and ESR1.

## Abstract

Genome-wide association studies (GWAS) have identified numerous genetic variants linked to breast cancer risk, but most discoveries come from European populations, limiting their applicability to other populations. Here, we show that the choice of genotype imputation reference panel, an essential step for GWAS, affects variant detection in Asian populations. Using two large breast cancer datasets from the Breast Cancer Association Consortium (n = 38 954 Asian samples), we compared the 1000 Genomes (1KG) reference panel with SG10K_Health (SG10K), an Asian-specific panel. SG10K imputed more rare variants and achieved higher accuracy for rare alleles (MAF < 0.001), while 1KG performed better for common variants in some contexts. Differences in panel performance influenced association signals, including breast cancer candidate loci such as FGFR2, TOX3, and ESR1. Together, these findings support the use of population-specific imputation panels as a means to improve variant discovery in underrepresented populations.