In:
Experimental Dermatology, Wiley, Vol. 29, No. 3 ( 2020-03), p. 243-253
Abstract:
Alopecia areata ( AA ) is a highly prevalent autoimmune disease that attacks the hair follicle and leads to hair loss that can range from small patches to complete loss of scalp and body hair. Our previous linkage and genome‐wide association studies ( GWAS ) generated strong evidence for aetiological contributions from inherited genetic variants at different population frequencies, including both rare mutations and common polymorphisms. Additionally, we conducted gene expression ( GE ) studies on scalp biopsies of 96 patients and controls to establish signatures of active disease. In this study, we performed an integrative analysis on these two datasets to test the hypothesis that rare CNV s in patients with AA could be leveraged to identify drivers of disease in our AA GE signatures. We analysed copy number variants ( CNV s) in a case‐control cohort of 673 patients with AA and 16 311 controls independent of the case‐control cohort of 96 research participants used in our GE study. Using an integrative computational analysis, we identified 14 genes whose expression levels were altered by CNV s in a consistent direction of effect, corresponding to gene expression changes in lesional skin of patients. Four of these genes were affected by CNV s in three or more unrelated patients with AA , including ATG 4B and SMARCA 2, which are involved in autophagy and chromatin remodelling, respectively. Our findings identified new classes of genes with potential contributions to AA pathogenesis.
Type of Medium:
Online Resource
ISSN:
0906-6705
,
1600-0625
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2026228-0
