Journal article
Integrative analysis of rare copy number variants and gene expression data in alopecia areata implicates an aetiological role for autophagy
Experimental dermatology, Vol.29(3), pp.243-253
03/01/2020
DOI: 10.1111/exd.13986
PMCID: PMC7213039
PMID: 31169925
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 CNVs in patients with AA could be leveraged to identify drivers of disease in our AA GE signatures. We analysed copy number variants (CNVs) 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 CNVs in a consistent direction of effect, corresponding to gene expression changes in lesional skin of patients. Four of these genes were affected by CNVs in three or more unrelated patients with AA, including ATG4B and SMARCA2, which are involved in autophagy and chromatin remodelling, respectively. Our findings identified new classes of genes with potential contributions to AA pathogenesis.
Details
- Title: Subtitle
- Integrative analysis of rare copy number variants and gene expression data in alopecia areata implicates an aetiological role for autophagy
- Creators
- Lynn Petukhova - Columbia UniversityAakash V. Patel - Columbia UniversityRachel K. Rigo - Columbia UniversityLi Bian - Columbia UniversityMiguel Verbitsky - Columbia UniversitySimone Sanna-Cherchi - Columbia UniversityStephanie O. Erjavec - Columbia UniversityAlexa R. Abdelaziz - Columbia UniversityJane E. Cerise - Columbia UniversityAli Jabbari - Columbia UniversityAngela M. Christiano - Columbia University
- Resource Type
- Journal article
- Publication Details
- Experimental dermatology, Vol.29(3), pp.243-253
- DOI
- 10.1111/exd.13986
- PMID
- 31169925
- PMCID
- PMC7213039
- NLM abbreviation
- Exp Dermatol
- ISSN
- 0906-6705
- eISSN
- 1600-0625
- Publisher
- Wiley
- Number of pages
- 11
- Grant note
- K08AR069111; P30AR069632; P50AR070588; R01AR065963; R01AR52579; R01AR56016 / National Institute of Arthritis and Musculoskeletal and Skin Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
- Language
- English
- Date published
- 03/01/2020
- Academic Unit
- Dermatology
- Record Identifier
- 9984296209802771
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