Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci
Betz, Regina C.
Price, Vera H.
de Jong, Annemieke
DeStefano, Gina M.
Amos, Christopher I.
Gregersen, Peter K.
de Bakker, Paul I. W.
Nöthen, Markus M.
Christiano, Angela M.Note: Order does not necessarily reflect citation order of authors.
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CitationBetz, R. C., L. Petukhova, S. Ripke, H. Huang, A. Menelaou, S. Redler, T. Becker, et al. 2015. “Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.” Nature communications 6 (1): 5966. doi:10.1038/ncomms6966. http://dx.doi.org/10.1038/ncomms6966.
AbstractAlopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in 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 MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed 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, TGFß/Tregs and JAK kinase signaling, and support the causal role of aberrant immune processes in AA.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17820804
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