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Lookup NU author(s): Dr Tee Siah
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s). Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.
Author(s): Tziotzios C, Petridis C, Dand N, Ainali C, Saklatvala JR, Pullabhatla V, Onoufriadis A, Pramanik R, Baudry D, Lee SH, Wood K, Liu L, Seegobin S, Michelotti GA, Lwin SM, Christou EAA, Curtis CJ, de Rinaldis E, Saxena A, Holmes S, Harries M, Palamaras I, Cunningham F, Parkins G, Kaur M, Farrant P, McDonagh A, Messenger A, Jones J, Jolliffe V, Ali I, Ardern-Jones M, Mitchell C, Burrows N, Atkar R, Banfield C, Alexandroff A, Champagne C, Cooper HL, Vano-Galvan S, Molina-Ruiz AM, Perez NO, Patel GK, Macbeth A, Page M, Bryden A, Mowbray M, Wahie S, Armstrong K, Cooke N, Goodfield M, Man I, de Berker D, Dunnill G, Takwale A, Rao A, Siah T-W, Sinclair R, Wade MS, Dlova NC, Setterfield J, Lewis F, Bhargava K, Kirkpatrick N, Estivill X, Stefanato CM, Flohr C, Spector T, Watt FM, Smith CH, Barker JN, Fenton DA, Simpson MA, McGrath JA
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 08/03/2019
Acceptance date: 13/02/2019
Date deposited: 20/03/2019
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
PubMed id: 30850646
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