Title
Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Human medicine
Engineering sciences. Technology
Source (journal)
Nature communications
Volume/pages
6(2015) , 8 p.
ISSN
2041-1723
2041-1723
Article Reference
5966
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ​ACOXL/​BCL2L11(​BIM) (2q13); ​GARP (​LRRC32) (11q13.5), as well as a third nominally significant region ​SH2B3(​LNK)/​ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/984bea/9308.pdf
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