Genomewide analysis of copy number variants in alopecia areata in a Central European cohort reveals association with MCHR2

Abstract

Alopecia areata (AA) is a common hair loss disorder of autoimmune aetiology, which often results in pronounced psychological distress. Understanding of the pathophysiology of AA is increasing, due in part to recent genetic findings implicating common variants at several genetic loci. To date, no study has investigated the contribution of copy number variants (CNVs) to AA, a prominent class of genomic variants involved in other autoimmune disorders. Here, we report a genomewide- and a candidate gene-focused CNV analysis performed in a cohort of 585 patients with AA and 1340 controls of Central European origin. A nominally significant association with AA was found for CNVs in the following five chromosomal regions: 4q35.2, 6q16.3, 9p23, 16p12.1 and 20p12.1. The most promising finding was a 342.5-kb associated region in 6q16.3 (duplications in 4/585 patients; 0/1340 controls). The duplications spanned the genes MCHR2 and MCHR2-AS1, implicated in melanin-concentrating hormone (MCH) signalling. These genes have not been implicated in previous studies of AA pathogenesis. However, previous research has shown that MCHR2 affects the scale colour of barfin flounder fish via the induction of melanin aggregation. AA preferentially affects pigmented hairs, and the hair of patients with AA frequently shows a change in colour when it regrows following an acute episode of AA. This might indicate a relationship between AA, pigmentation and MCH signalling. In conclusion, the present results provide suggestive evidence for the involvement of duplications in MCHR2 in AA pathogenesis.

Alopecia areata

“…The emergence of these signatures further refined the focus using small-molecule JAK inhibitors. Recently, associations between alopecia areata and copy number variations (CNV) were found using genome-wide scans (Box 3) 59 .…”

Integrative analysis of rare copy number variants and gene expression data in alopecia areata implicates an aetiological role for autophagy

“…While CNVs are present in every human genome, burden analyses in cohorts of congenital disorders have shown that affected patients are more likely to harbour large gene‐disrupting (genic) CNVs than unaffected individuals . Likewise, common CNVs have been identified in association studies of autoimmune diseases such as Crohn's disease, systemic lupus erythematosus (SLE), psoriasis, rheumatoid arthritis (RA), type 1 diabetes, and AA …”

AAD Forschungspreis 2018

“…Das Team Johannes Fischer/PD Dr. med. Franziska Degenhardt vom Institut für Humangenetik in Bonn hat zum ersten Mal mit molekulargenetischen Methoden eine bestimmte, mit dem Melanin‐Stoffwechsel in Zusammenhang stehende Region im menschlichen Genom als Risikofaktor für die Erkrankung identifizieren können . Frau Dr. rer.…”