To verify that the ESR1 binding site is enriched in the 476 target genes of 6q25 risk locus, we randomly sampled the entire genome 1 million times, each time we pick up 476 genes and counted the the occurence of ESR1 binding site in the putative enhancer regions (1kb to 50kb) according to ChIPseq study. Then we compare the number of ESR1 binding site found in the radom gene sets to that of the 476 6q25 target genes to compute a simulated P value for enrichment.