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

Tziotzios, Christos and Petridis, Christos and Dand, Nick and Ainali, Chrysanthi and Saklatvala, Jake R and Pullabhatla, Venu and Onoufriadis, Alexandros and Pramanik, Rashida and Baudry, David and Lee, Sang Hyuck and Wood, Kristie and Liu, Lu and Seegobin, Seth and Michelotti, Gregory A and Lwin, Su M and Christou, Evangelos A A and Curtis, Charles J and de Rinaldis, Emanuele and Saxena, Alka and Holmes, Susan and Harries, Matthew and Palamaras, Ioulios and Cunningham, Fiona and Parkins, Gregory and Kaur, Manjit R and Farrant, Paul and McDonagh, Andrew and Messenger, Andrew and Jones, Jennifer and Jolliffe, Victoria and Ali, Iaisha and Ardern-Jones, Michael and Mitchell, Charles and Burrows, Nigel and Atkar, Ravinder and Banfield, Cedric and Alexandroff, Anton and Champagne, Caroline and Cooper, Hywel L and Vañó-Galván, Sergio and Molina-Ruiz, Ana Maria and Perez, Nerea Ormaechea and Patel, Girish K and Macbeth, Abby and Page, Melanie and Bryden, Alyson and Mowbray, Megan and Wahie, Shyamal and Armstrong, Keith and Cooke, Nicola and Goodfield, Mark and Man, Irene and de Berker, David and Dunnill, Giles and Takwale, Anita and Rao, Archana and Siah, Tee-Wei and Sinclair, Rodney and Wade, Martin S and Dlova, Ncoza C and Setterfield, Jane and Lewis, Fiona and Bhargava, Kapil and Kirkpatrick, Niall and Estivill, Xavier and Stefanato, Catherine M and Flohr, Carsten and Spector, Timothy and Watt, Fiona M and Smith, Catherine H and Barker, Jonathan N and Fenton, David A and Simpson, Michael A and McGrath, John A (2019) Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02. Nature communications, 10 (1). p. 1150. ISSN 2041-1723. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

[img]
Preview
Text
s41467-019-09117-w.pdf - Published Version
Available under License Creative Commons Attribution 4.0.

Download (1MB) | Preview
Official URL: https://www.nature.com/articles/s41467-019-09117-w

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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WR Skin. Dermatology
Divisions: Ambulatory Care > Dermatology
Related URLs:
Depositing User: Miss Emily Johnson
Date Deposited: 15 Mar 2019 14:23
Last Modified: 15 Mar 2019 14:23
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1922

Actions (login required)

View Item View Item