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Background  Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the function of these non-coding risk loci is critical to elucidate the genetic susceptibility to prostate cancer.    Results  We generate genome-wide regulatory element maps and performed genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and tumorigenic prostate cells. Using this information, we annotate the regulatory potential of 2,181 fine-mapped prostate cancer risk-associated SNPs and predict a set of target genes that are regulated by prostate cancer risk-related H3K27Ac-mediated loops. We next identify prostate cancer risk-associated CTCF sites involved in long-range chromatin loops. We use CRISPR-mediated deletion to remove prostate cancer risk-associated CTCF anchor regions and the CTCF anchor regions looped to the prostate cancer risk-associated CTCF sites, and we observe up to 100-fold increases in expression of genes within the loops when the prostate cancer risk-associated CTCF anchor regions are deleted.    Conclusions  We identify GWAS risk loci involved in long-range loops that function to repress gene expression within chromatin loops. Our studies provide new insights into the genetic susceptibility to prostate cancer.    Electronic supplementary material  The online version of this article (10.1186/s13059-018-1531-0) contains supplementary material, which is available to authorized users.

CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops