1. Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02
- Author
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Paul Farrant, Mark Goodfield, Catherine H. Smith, V. Jolliffe, Gregory Parkins, Caroline Champagne, Lu Liu, Nigel Burrows, A. S. Bryden, Kristie Wood, Anton B. Alexandroff, Irene Man, Alka Saxena, Su M. Lwin, Iaisha Ali, Catherine M. Stefanato, Kapil Bhargava, Sang Hyuck Lee, Melanie Page, Xavier Estivill, Tim D. Spector, Carsten Flohr, Susan Holmes, David de Berker, A. E. Macbeth, Ncoza C. Dlova, David Baudry, Jake Saklatvala, Nerea Ormaechea Perez, Archana Rao, David A. Fenton, Martin S Wade, Cedric Charles Banfield, Jennifer Jones, Evangelos A A Christou, Ravinder Atkar, Gregory A Michelotti, Sergio Vano-Galvan, Seth D. Seegobin, Jane Setterfield, Jonathan Barker, Chrysanthi Ainali, Christos Tziotzios, Charles Curtis, Rashida Pramanik, Matthew Harries, Girish K Patel, Niall Kirkpatrick, Venu Pullabhatla, Fiona Cunningham, Nick Dand, Hywel L Cooper, Rodney Sinclair, Keith Armstrong, Emanuele de Rinaldis, Andrew J. G. McDonagh, M R Kaur, Fiona Lewis, Michael A. Simpson, John A. McGrath, Charles E. Mitchell, Nicola Cooke, Fiona M. Watt, Alexandros Onoufriadis, Michael R. Ardern-Jones, Tee-Wei Siah, Ioulios Palamaras, Ana María Molina-Ruiz, Megan Mowbray, A. Takwale, Andrew G. Messenger, Giles Dunnill, Christos Petridis, and Shyamal Wahie
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0301 basic medicine ,Science ,General Physics and Astronomy ,Gene Expression ,Locus (genetics) ,Genome-wide association study ,02 engineering and technology ,Biology ,Adaptive Immunity ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cohort Studies ,03 medical and health sciences ,HLA-B7 Antigen ,medicine ,Missense mutation ,Humans ,Genetic Predisposition to Disease ,Allele ,lcsh:Science ,Genetic association ,Genetics ,Multidisciplinary ,integumentary system ,Genome, Human ,Frontal fibrosing alopecia ,Case-control study ,Alopecia ,General Chemistry ,021001 nanoscience & nanotechnology ,medicine.disease ,Immunity, Innate ,3. Good health ,stomatognathic diseases ,030104 developmental biology ,Hair loss ,Genetic Loci ,Case-Control Studies ,Cytochrome P-450 CYP1B1 ,Female ,lcsh:Q ,0210 nano-technology ,Transcriptome ,Genome-Wide Association Study - 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., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.
- Published
- 2019
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