Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Abstract

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.

Metadata

Item Type:	Article
Authors/Creators:	Tziotzios, C. Petridis, C. Dand, N. Ainali, C. Saklatvala, J.R. Pullabhatla, V. Onoufriadis, A. Pramanik, R. Baudry, D. Lee, S.H. Wood, K. Liu, L. Seegobin, S. Michelotti, G.A. Lwin, S.M. Christou, E.A.A. Curtis, C.J.. 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, H.L. Vano-Galvan, S. Maria Molina-Ruiz, A. Ormaechea Perez, N. Patel, G.K. 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, M.S. Dlova, N.C. Setterfield, J. Lewis, F. Bhargava, K. Kirkpatrick, N. Estivill, X. Stefanato, C.M. Flohr, C. Spector, T. Watt, F.M. Smith, C.H. Barker, J.N. Fenton, D.A. Simpson, M.A. McGrath, J.A.
Copyright, Publisher and Additional Information:	© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 13 February 2019 Published (online): 8 March 2019 Published: 8 March 2019
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	01 Jul 2019 14:57
Last Modified:	01 Jul 2019 15:12
Status:	Published
Publisher:	Nature Research
Refereed:	Yes
Identification Number:	10.1038/s41467-019-09117-w
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:147887

CORE (COnnecting REpositories)

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Abstract

Metadata

Download

Published Version

Export

Statistics