Chromatin looping links target genes with genetic risk loci for dermatological traitsCitation formats
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Chromatin looping links target genes with genetic risk loci for dermatological traits. / Shi, Chenfu; Ray-Jones, Helen; Ding, James; Duffus, Kate; Fu, Yao ; Gaddi, Vasanthipriyadarshini; Gough, Oliver; Hankinson, Jenny; Martin, Paul; Mcgovern, Amanda; Yarwood, Annie; Gaffney, Patrick ; Eyre, Stephen; Rattray, Magnus; Warren , Richard B; Orozco, Gisela.
In: The Journal of Investigative Dermatology, Vol. 141, No. 8, 2021, p. 1975-1984.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Chromatin looping links target genes with genetic risk loci for dermatological traits
AU - Shi, Chenfu
AU - Ray-Jones, Helen
AU - Ding, James
AU - Duffus, Kate
AU - Fu, Yao
AU - Gaddi, Vasanthipriyadarshini
AU - Gough, Oliver
AU - Hankinson, Jenny
AU - Martin, Paul
AU - Mcgovern, Amanda
AU - Yarwood, Annie
AU - Gaffney, Patrick
AU - Eyre, Stephen
AU - Rattray, Magnus
AU - Warren , Richard B
AU - Orozco, Gisela
PY - 2021
Y1 - 2021
N2 - 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 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, 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.
AB - 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 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, 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.
U2 - 10.1016/j.jid.2021.01.015
DO - 10.1016/j.jid.2021.01.015
M3 - Article
VL - 141
SP - 1975
EP - 1984
JO - The Journal of Investigative Dermatology
JF - The Journal of Investigative Dermatology
SN - 0022-202X
IS - 8
ER -