Background Genome-wide association studies have identified 196 high confidence independent signals associated with breast cancer susceptibility. Variants within these signals frequently fall in distal regulatory DNA elements that control gene expression. Results We designed a Capture Hi-C array to enrich for chromatin interactions between the credible causal variants and target genes in six human mammary epithelial and breast cancer cell lines. We show that interacting regions are enriched for open chromatin, histone marks for active enhancers, and transcription factors relevant to breast biology. We exploit this comprehensive resource to identify candidate target genes at 139 independent breast cancer risk signals and explore the functional mechanism underlying altered risk at the 12q24 risk region. Conclusions Our results demonstrate the power of combining genetics, computational genomics, and molecular studies to rationalize the identification of key variants and candidate target genes at breast cancer GWAS signals.

中文翻译：

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139 个独立乳腺癌风险信号的染色质相互作用组图谱

背景 全基因组关联研究已经确定了 196 个与乳腺癌易感性相关的高可信度独立信号。这些信号中的变异经常落在控制基因表达的远端调控 DNA 元件中。结果 我们设计了一个 Capture Hi-C 阵列来丰富六种人类乳腺上皮和乳腺癌细胞系中可信的因果变异和靶基因之间的染色质相互作用。我们表明相互作用区域富含开放染色质、活性增强子的组蛋白标记和与乳腺生物学相关的转录因子。我们利用这一综合资源在 139 个独立的乳腺癌风险信号中识别候选靶基因，并探索 12q24 风险区域风险改变的潜在功能机制。