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Nature Research, Nature Communications, 1(10), 2019

DOI: 10.1038/s41467-019-09117-w

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

Journal article published in 2019 by Christos Tziotzios ORCID, Christos Petridis, Nick Dand ORCID, Chrysanthi Ainali, Jake R. Saklatvala, Venu Pullabhatla, Alexandros Onoufriadis, Rashida Pramanik, David Baudry, Sang Hyuck Lee, Kristie Wood, Lu Liu, Seth Seegobin, Gregory A. Michelotti, Su M. Lwin and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractFrontal 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.