Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2025

Journal

Nature Genetics

DOI

10.1038/s41588-024-02031-y

PMID

39753771

PMCID

PMC12184877

PubMedCentral® Posted Date

1-3-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 and Wnt/β-catenin pathways. Single-cell RNA sequencing or in vitro experiment data provided additional functional evidence for 105 genes. Our study uncovered large numbers of association signals and candidate susceptibility genes for breast cancer, uncovered breast cancer genetics and biology, and supported the value of including multi-ancestry data in fine-mapping analyses.

Keywords

Female, Humans, Asian People, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Risk Factors, White People, Black People, breast cancer, GWAS, fine-mapping, risk loci, susceptibility gene, multi-ancestry

Published Open-Access

yes

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