Genomewide analysis of copy number variants in alopecia areata in a Central European cohort reveals association with MCHR2.
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.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Johannes
J
Fischer
Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Franziska
F
Degenhardt
Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Andrea
A
Hofmann
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Silke
S
Redler
Institute of Human Genetics, University of Bonn, Bonn, Germany.
F Buket
FB
Basmanav
Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Stefanie
S
Heilmann-Heimbach
Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany.
Sandra
S
Hanneken
Department of Dermatology, University of Munich, Munich, Germany.
Kathrin A
KA
Giehl
Department of Dermatology, University of Munich, Munich, Germany.
Hans
H
Wolff
Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Duisburg, Germany.
Susanne
S
Moebus
Dermatological Practice, Paderborn, Germany.
Roland
R
Kruse
Hair & Nail, Dermatological Practice, Wesseling, Germany.
Gerhard
G
Lutz
Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium.
Bettina
B
Blaumeiser
Department of Dermatology, University of Münster, Münster, Germany.
Markus
M
Böhm
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Natalie
N
Garcia Bartels
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ulrike
U
Blume-Peytavi
Department of Dermatology, Columbia University, New York, NY, USA.
Lynn
L
Petukhova
Department of Dermatology, Columbia University, New York, NY, USA.|Department of Genetics and Development, Columbia University, New York, NY, USA.
Angela M
AM
Christiano
Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Markus M
MM
Nöthen
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Regina C
0000-0001-5024-3623
RC
Betz
D000328:Adult; D000506:Alopecia Areata / Q000235:genetics*; D001530:Belgium; D002874:Chromosome Mapping; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005060:Europe; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D007028:Hypothalamic Hormones / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D009426:Netherlands; D010858:Pigmentation; D010907:Pituitary Hormones / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011979:Receptors, Pituitary Hormone / Q000235:genetics*; D015398:Signal Transduction
D007028:Hypothalamic Hormones; C431280:MCHR2 protein, human; D008543:Melanins; D010907:Pituitary Hormones; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone; C019463:melanin-concentrating hormone
MCHR2; alopecia areata; copy number variants; genetic complex disorder; molecular genetics