Capture Hi-C identifies putative target genes at 33 breast cancer risk loci.

Baxter JS1, Leavy OC2,3, Dryden NH1, Maguire S1, Johnson N1, Fedele V1, Simigdala N1, Martin LA1, Andrews S4, Wingett SW4, Assiotis I5, Fenwick K5, Chauhan R1, Rust AG1, Orr N1, Dudbridge F2,3, Haider S6, Fletcher O7.

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Abstract

Genome-wide association studies (GWAS) have identified approximately 100 breast cancer risk loci. Translating these findings into a greater understanding of the mechanisms that influence disease risk requires identification of the genes or non-coding RNAs that mediate these associations. Here, we use Capture Hi-C (CHi-C) to annotate 63 loci; we identify 110 putative target genes at 33 loci. To assess the support for these target genes in other data sources we test for associations between levels of expression and SNP genotype (eQTLs), disease-specific survival (DSS), and compare them with somatically mutated cancer genes. 22 putative target genes are eQTLs, 32 are associated with DSS and 14 are somatically mutated in breast, or other, cancers. Identifying the target genes at GWAS risk loci will lead to a greater understanding of the mechanisms that influence breast cancer risk and prognosis.