Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.

Détails

ID Serval
serval:BIB_66D42C2EEBC6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.
Périodique
Journal of Investigative Dermatology
Auteur(s)
Heilmann S., Kiefer A.K., Fricker N., Drichel D., Hillmer A.M., Herold C., Tung J.Y., Eriksson N., Redler S., Betz R.C., Li R., Kárason A., Nyholt D.R., Song K., Vermeulen S.H., Kanoni S., Dedoussis G., Martin N.G., Kiemeney L.A., Mooser V., Stefansson K., Richards J.B., Becker T., Brockschmidt F.F., Hinds D.A., Nöthen M.M.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Statut éditorial
Publié
Date de publication
2013
Volume
133
Numéro
6
Pages
1489-1496
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10(-8)<P<10(-5)) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10(-15)) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.
Mots-clé
Adult, Alopecia/epidemiology, Alopecia/etiology, Cholestanetriol 26-Monooxygenase/genetics, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 5, European Continental Ancestry Group/genetics, European Continental Ancestry Group/statistics & numerical data, Frizzled Receptors/genetics, Genetic Predisposition to Disease/epidemiology, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide/genetics, Risk Factors, Wnt Proteins/genetics, Wnt Signaling Pathway/physiology, Wnt3 Protein/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/03/2012 9:44
Dernière modification de la notice
20/08/2019 14:22
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