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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Christos Tziotzios, Christos Petridis, Nick Dand, 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, Evangelos A. A. Christou, Charles J. Curtis, Emanuele de Rinaldis, Alka Saxena, Susan Holmes, Matthew Harries, Ioulios Palamaras, Fiona Cunningham, Gregory Parkins, Manjit Kaur, Paul Farrant, Andrew McDonagh, Andrew Messenger, Jennifer Jones, Victoria Jolliffe, Iaisha Ali, Michael Ardern-Jones, Charles Mitchell, Nigel Burrows, Ravinder Atkar, Cedric Banfield, Anton Alexandroff, Caroline Champagne, Hywel L. Cooper, Sergio Vañó-Galván, Ana Maria Molina-Ruiz, Nerea Ormaechea Perez, Girish K. Patel, Abby Macbeth, Melanie Page, Alyson Bryden, Megan Mowbray, Shyamal Wahie, Keith Armstrong, Nicola Cooke, Mark Goodfield, Irene Man, David de Berker, Giles Dunnill, Anita Takwale, Archana Rao, Tee-Wei Siah, Rodney Sinclair, Martin S. Wade, Ncoza C. Dlova, Jane Setterfield, Fiona Lewis, Kapil Bhargava, Niall Kirkpatrick, Xavier Estivill, Catherine M. Stefanato, Carsten Flohr, Timothy Spector, Fiona M. Watt, Catherine H. Smith, Jonathan N. Barker, David A. Fenton, Michael A. Simpson, John A. McGrath

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. More... »

PAGES

1150

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09117-w

DOI

http://dx.doi.org/10.1038/s41467-019-09117-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112641448

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30850646


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