Chromatin looping links target genes with genetic risk loci for dermatological traits

Chromatin looping between regulatory elements and gene promoters presents a potential mechanism whereby disease risk variants affect their target genes. Here we use H3K27ac HiChIP, a method for assaying the active chromatin interactome in two cell lines: keratinocytes and skin derived CD8+ T cells. We integrate public datasets for a lymphoblastoid cell line and primary CD4+ T cells and identify gene targets at risk loci for skin-related disorders. Interacting genes enrich for pathways of known importance in each trait, such as cytokine response (psoriatic arthritis, psoriasis) and replicative senescence (melanoma). We show examples of how our analysis can inform changes in the current understanding of multiple psoriasis associated risk loci. For example, the variant rs10794648, which is generally assigned to IFNLR1, was linked to GRHL3 in our dataset, a gene essential in skin repair and development. Our findings, therefore, indicate a renewed importance of skin related factors in the risk of disease. HiChIP and Hi-C data was generated for Keratinocytes (HaCaT) and CD8+ T cells (MyLa). Keratinocytes were also stimulated with IFN-?. We generated biological 2 replicates for each HiChIP sample and 1 replicate for each Hi-C sample. Accompanying RNA-seq data was also generated with 4 libraries for naive HaCaT, 3 for stimulated HaCaT, 1 for MyLa and 2 for GM12878 cells. The data was also uploaded to GSE68257 for a previous study but the processed files here are updated to reflect the new study.