TY  - JOUR
AU  - Heilmann, Stefanie
AU  - Kiefer, Amy K
AU  - Fricker, Nadine
AU  - Drichel, Dmitriy
AU  - Hillmer, Axel M
AU  - Herold, Christine
AU  - Tung, Joyce Y
AU  - Eriksson, Nicholas
AU  - Redler, Silke
AU  - Betz, Regina C
AU  - Li, Rui
AU  - Kárason, Ari
AU  - Nyholt, Dale R
AU  - Song, Kijoung
AU  - Vermeulen, Sita H
AU  - Kanoni, Stavroula
AU  - Dedoussis, George
AU  - Martin, Nicholas G
AU  - Kiemeney, Lambertus A
AU  - Mooser, Vincent
AU  - Stefansson, Kari
AU  - Richards, J Brent
AU  - Becker, Tim
AU  - Brockschmidt, Felix F
AU  - Hinds, David A
AU  - Nöthen, Markus M
TI  - Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.
JO  - The journal of investigative dermatology
VL  - 133
IS  - 6
SN  - 0022-202X
CY  - Amsterdam
PB  - Elsevier
M1  - DZNE-2020-03236
SP  - 1489-1496
PY  - 2013
AB  - 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.
KW  - Adult
KW  - Alopecia: epidemiology
KW  - Alopecia: etiology
KW  - Alopecia: genetics
KW  - Alopecia: metabolism
KW  - Cholestanetriol 26-Monooxygenase: genetics
KW  - Chromosomes, Human, Pair 12
KW  - Chromosomes, Human, Pair 2
KW  - Chromosomes, Human, Pair 3
KW  - Chromosomes, Human, Pair 5
KW  - European Continental Ancestry Group: genetics
KW  - European Continental Ancestry Group: statistics & numerical data
KW  - Frizzled Receptors: genetics
KW  - Genetic Predisposition to Disease: epidemiology
KW  - Genetic Predisposition to Disease: genetics
KW  - Genome-Wide Association Study
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Polymorphism, Single Nucleotide: genetics
KW  - Risk Factors
KW  - Wnt Proteins: genetics
KW  - Wnt Signaling Pathway: physiology
KW  - Wnt3 Protein: genetics
KW  - FZD10 protein, human (NLM Chemicals)
KW  - Frizzled Receptors (NLM Chemicals)
KW  - WNT10A protein, human (NLM Chemicals)
KW  - WNT3 protein, human (NLM Chemicals)
KW  - WNT6 protein, human (NLM Chemicals)
KW  - Wnt Proteins (NLM Chemicals)
KW  - Wnt3 Protein (NLM Chemicals)
KW  - CYP27A1 protein, human (NLM Chemicals)
KW  - Cholestanetriol 26-Monooxygenase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23358095
DO  - DOI:10.1038/jid.2013.43
UR  - https://pub.dzne.de/record/136914
ER  -