Integrative Omics Analysis Reveals Functional Variants of Hemoglobin Zeta (HBZ) as an Ancestry-Specific Risk Factor for Triple-Negative Breast Cancer

BackgroundTriple-negative breast cancer (TNBC) disproportionately affects women of African ancestry, yet the biological mechanisms underlying this disparity remain poorly understood. While recent genome-wide association studies (GWAS) have identified numerous TNBC risk variants, their functional consequences have not been systematically evaluated in African-ancestry populations. We hypothesized that ancestry-specific regulatory variants drive distinct transcriptomic and proteomic landscapes that contribute to TNBC aggressiveness. MethodsWe extracted 2,849 unique TNBC-associated variants (p-value [≤] 1x10{square}{square}) from the GWAS Catalog. Of these, 206 were excluded due to absence in our whole-genome sequencing (WGS) dataset or low minor allele frequency ( View larger version (69K): org.highwire.dtl.DTLVardef@ba0dd4org.highwire.dtl.DTLVardef@e1ddc5org.highwire.dtl.DTLVardef@a6e962org.highwire.dtl.DTLVardef@2438db_HPS_FORMAT_FIGEXP M_FIG C_FIG