Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.

Nat Commun
Authors
Keywords
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.

Year of Publication
2015
Journal
Nat Commun
Volume
6
Pages
5966
Date Published
2015 Jan 22
ISSN
2041-1723
URL
DOI
10.1038/ncomms6966
PubMed ID
25608926
PubMed Central ID
PMC4451186
Links
Grant list
R01 AR052579 / AR / NIAMS NIH HHS / United States
N01AR62279 / HL / NHLBI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
R01AR56016 / AR / NIAMS NIH HHS / United States
T32 GM007088 / GM / NIGMS NIH HHS / United States
R01AR52579 / AR / NIAMS NIH HHS / United States
P30 CA023108 / CA / NCI NIH HHS / United States
N01AR62279 / AR / NIAMS NIH HHS / United States
U01 AR067173 / AR / NIAMS NIH HHS / United States
R01 AR056016 / AR / NIAMS NIH HHS / United States