This study reports the results of a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry, and 14,068 cases and 13,104 controls of East Asian ancestry. The researchers identified 65 new loci associated with overall breast cancer risk at a significance level of *P* < 5 × 10^−8^. These loci predominantly contain distal regulatory elements, and the study demonstrates a strong overlap between candidate target genes and somatic driver genes in breast tumors. The heritability of breast cancer due to all single-nucleotide polymorphisms (SNPs) in regulatory features was 2–5-fold enriched relative to the genome-wide average, with significant enrichment for particular transcription factor binding sites. The findings provide further insights into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.This study reports the results of a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry, and 14,068 cases and 13,104 controls of East Asian ancestry. The researchers identified 65 new loci associated with overall breast cancer risk at a significance level of *P* < 5 × 10^−8^. These loci predominantly contain distal regulatory elements, and the study demonstrates a strong overlap between candidate target genes and somatic driver genes in breast tumors. The heritability of breast cancer due to all single-nucleotide polymorphisms (SNPs) in regulatory features was 2–5-fold enriched relative to the genome-wide average, with significant enrichment for particular transcription factor binding sites. The findings provide further insights into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.