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Nat Commun. 2019 Mar 8;10(1):1150. doi: 10.1038/s41467-019-09117-w.

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

Author information

1
St. John's Institute of Dermatology, King's College London, London, Guy's Hospital, London, SE1 9RT, UK. christos.tziotzios@kcl.ac.uk.
2
Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, SE1 9RT, UK.
3
St. John's Institute of Dermatology, King's College London, London, Guy's Hospital, London, SE1 9RT, UK.
4
UK NIHR GSTFT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, SE1 9RT, UK.
5
NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust (SLaM) & Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, Denmark Hill Campus, London, SE5 8EF, UK.
6
National Diagnostic EB Laboratory, St. Thomas Hospital, London, SE1 7EH, UK.
7
Metabolon, Inc., Morrisville, NC, 27560, USA.
8
Alan Lyell Centre for Dermatology, Queen Elizabeth University Hospital, Glasgow, G51 4TF, UK.
9
The Dermatology Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Salford, M6 8HD, UK.
10
Department of Dermatology, Barnet General Hospital, Royal Free Foundation Trust, London, EN5 3DJ, UK.
11
Department of Dermatology, Solihull Hospital, Solihull, B91 2JL, UK.
12
Department of Dermatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, BN2 3EW, UK.
13
Department of Dermatology, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.
14
Department of Dermatology, Royal Free Hospital, London, NW3 2QG, UK.
15
Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, E1 1BB, UK.
16
Department of Dermatology, Imperial College Healthcare NHS Trust, London, W12 0HS, UK.
17
Department of Dermatology, University Hospitals Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.
18
Department of Dermatology, Portsmouth Hospitals NHS Trust, Portsmouth, PO6 3LY, UK.
19
Department of Dermatology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK.
20
Department of Dermatology, Peterborough City Hospital, Peterborough, PE3 9GZ, UK.
21
Department of Dermatology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, LE3 9QP, UK.
22
Department of Dermatology, The Churchill Hospital, Oxford, OX3 7LE, UK.
23
Trichology Unit, Dermatology Department, Ramon Y Cajal Hospital, University of Alcala, IRYCIS, Madrid, 28034, Spain.
24
Hospital Universitario Fundación Jiménez Díaz, Madrid, 28040, Spain.
25
Department of Dermatology, Hospital Donostia, San Sebastian, 20014, Spain.
26
Hywel Dda University Health Board, Cardiff, SA31 3BB, UK.
27
Department of Dermatology, Norfolk & Norwich University Hospitals NHS Foundation Trust, Norwich, NR4 7UY, UK.
28
Department of Dermatology, Ninewells Hospital, Dundee, DD1 9SY, UK.
29
Department of Dermatology, Queen Margaret Hospital, Dunfermline, KY12 0SU, UK.
30
Department of Dermatology, County Durham and Darlington NHS Foundation Trust, Darlington, DL3 6HX, UK.
31
Department of Dermatology, Royal Victoria Hospital, Belfast, BT12 6BA, UK.
32
Department of Dermatology, Whiteabbey Hospital, Northern Health & Social Care Trust, Co Antrim, BT37 9RH, UK.
33
Department of Dermatology, Chapel Allerton Hospital, Leeds teaching Hospitals NHS Trust, Leeds, LS7 4SA, UK.
34
Department of Dermatology, Surrey and Sussex Healthcare NHS Trust, Surrey, RH1 5RH, UK.
35
Department of Dermatology, University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
36
Department of Dermatology, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, GL1 3NN, UK.
37
Department of Dermatology, Kingston Hospital NHS Foundation Trust, Kingston-upon-Thames, KT2 7QB, UK.
38
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.
39
Department of Dermatology, University of Melbourne, Melbourne, VIC 3010, Australia.
40
The London Skin and Hair Clinic, London, WC1V 7DN, UK.
41
Department of Dermatology, School of Clinical Medicine, Nelson R Mandela School of Medicine, Durban, 4001, South Africa.
42
Craniofacial Surgery Unit, Chelsea & Westminster Hospital, London, SW10 9NH, UK.
43
Genetics Unit, Dexeus Women's Health, Barcelona, 08028, Spain.
44
Department of Dermatopathology, St. John's Institute of Dermatology, St. Thomas' Hospital, London, SE1 7EH, UK.
45
The Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
46
Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London, SE1 9RT, UK.
47
St. John's Institute of Dermatology, King's College London, London, Guy's Hospital, London, SE1 9RT, UK. john.mcgrath@kcl.ac.uk.

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.

PMID:
30850646
PMCID:
PMC6408457
DOI:
10.1038/s41467-019-09117-w
[Indexed for MEDLINE]
Free PMC Article

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