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. In this study, we use H3K27ac HiChIP, a method for assaying the active chromatin interactome in two cell lines: keratinocytes and skin lymphoma-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 and 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, a gene essential in skin repair and development, in our dataset. Our findings, therefore, indicate a renewed importance of skin-related factors in the risk of disease.

Automated summary

Chromatin looping plays a potential role in how disease risk variants impact target genes. Using the H3K27ac HiChIP method, the study identified gene targets at risk loci for skin-related disorders and highlighted the importance of skin-related factors in disease risk. The findings suggest a new understanding of multiple psoriasis-associated risk loci.