Allele specific chromatin interaction of 9p21 endometriosis risk locus regulates expression level of ANRIL

We explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging allele-specific functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter.