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

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02
Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02
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.
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Tziotzios, Christos, Petridis, Christos, Dand, Nick, Ainali, Chrysanthi, Saklatvala, Jake R., Pullabhatla, Venu, Onoufriadis, Alexandros, Pramanik, Rashida, Baudry, David, Lee, Sang Hyuck, Wood, Kristie, Liu, Lu, Seegobin, Seth, Michelotti, Gregory A., Lwin, Su M., Christou, Evangelos A. A., Curtis, Charles J., De Rinaldis, Emanuele, Saxena, Alka, Holmes, Susan, Harries, Matthew, Palamaras, Ioulios, Cunningham, Fiona, Parkins, Gregory, Kaur, Manjit, Farrant, Paul, Mcdonagh, Andrew, Messenger, Andrew, Jones, Jennifer, Jolliffe, Victoria, Ali, Iaisha, Ardern-Jones, Michael, Mitchell, Charles, Burrows, Nigel, Atkar, Ravinder, Banfield, Cedric, Alexandroff, Anton, Champagne, Caroline, Cooper, Hywel L., Vañó-galván, Sergio, Molina-ruiz, Ana Maria, Perez, Nerea Ormaechea, Patel, Girish K., Macbeth, Abby, Page, Melanie, Bryden, Alyson, Mowbray, Megan, Wahie, Shyamal, Armstrong, Keith, Cooke, Nicola, Goodfield, Mark, Man, Irene, De Berker, David, Dunnill, Giles, Takwale, Anita, Rao, Archana, Siah, Tee-wei, Sinclair, Rodney, Wade, Martin S., Dlova, Ncoza C., Setterfield, Jane, Lewis, Fiona, Bhargava, Kapil, Kirkpatrick, Niall, Estivill, Xavier, Stefanato, Catherine M., Flohr, Carsten, Spector, Timothy, Watt, Fiona M., Smith, Catherine H., Barker, Jonathan N., Fenton, David A., 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), [1150]. (doi:10.1038/s41467-019-09117-w).

Record type: Article

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.

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Accepted/In Press date: 13 February 2019
e-pub ahead of print date: 8 March 2019
Published date: 1 December 2019

Identifiers

Local EPrints ID: 428819
URI: http://eprints.soton.ac.uk/id/eprint/428819
PURE UUID: f9cebbda-5d65-4c67-9643-5d74ffd87acd

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Date deposited: 11 Mar 2019 17:30
Last modified: 10 Jan 2022 05:43

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Contributors

Author: Christos Tziotzios
Author: Christos Petridis
Author: Nick Dand
Author: Chrysanthi Ainali
Author: Jake R. Saklatvala
Author: Venu Pullabhatla
Author: Alexandros Onoufriadis
Author: Rashida Pramanik
Author: David Baudry
Author: Sang Hyuck Lee
Author: Kristie Wood
Author: Lu Liu
Author: Seth Seegobin
Author: Gregory A. Michelotti
Author: Su M. Lwin
Author: Evangelos A. A. Christou
Author: Charles J. Curtis
Author: Emanuele De Rinaldis
Author: Alka Saxena
Author: Susan Holmes
Author: Matthew Harries
Author: Ioulios Palamaras
Author: Fiona Cunningham
Author: Gregory Parkins
Author: Manjit Kaur
Author: Paul Farrant
Author: Andrew Mcdonagh
Author: Andrew Messenger
Author: Jennifer Jones
Author: Victoria Jolliffe
Author: Iaisha Ali
Author: Charles Mitchell
Author: Nigel Burrows
Author: Ravinder Atkar
Author: Cedric Banfield
Author: Anton Alexandroff
Author: Caroline Champagne
Author: Hywel L. Cooper
Author: Sergio Vañó-galván
Author: Ana Maria Molina-ruiz
Author: Nerea Ormaechea Perez
Author: Girish K. Patel
Author: Abby Macbeth
Author: Melanie Page
Author: Alyson Bryden
Author: Megan Mowbray
Author: Shyamal Wahie
Author: Keith Armstrong
Author: Nicola Cooke
Author: Mark Goodfield
Author: Irene Man
Author: David De Berker
Author: Giles Dunnill
Author: Anita Takwale
Author: Archana Rao
Author: Tee-wei Siah
Author: Rodney Sinclair
Author: Martin S. Wade
Author: Ncoza C. Dlova
Author: Jane Setterfield
Author: Fiona Lewis
Author: Kapil Bhargava
Author: Niall Kirkpatrick
Author: Xavier Estivill
Author: Catherine M. Stefanato
Author: Carsten Flohr
Author: Timothy Spector
Author: Fiona M. Watt
Author: Catherine H. Smith
Author: Jonathan N. Barker
Author: David A. Fenton
Author: Michael A. Simpson
Author: John A. Mcgrath

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