Journal Article

DZNE-2020-03236

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.

Heilmann, S. ; Kiefer, A. K. ; Fricker, N. ; Drichel, D.DZNE* ; Hillmer, A. M. ; Herold, C.DZNE* ; 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.DZNE* ; Brockschmidt, F. F. ; Hinds, D. A. ; Nöthen, M. M. (Corresponding author)

2013
Elsevier Amsterdam

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Please use a persistent id in citations: doi:10.1038/jid.2013.43

Abstract: 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.

Keyword(s): Adult (MeSH) ; Alopecia: epidemiology (MeSH) ; Alopecia: etiology (MeSH) ; Alopecia: genetics (MeSH) ; Alopecia: metabolism (MeSH) ; Cholestanetriol 26-Monooxygenase: genetics (MeSH) ; Chromosomes, Human, Pair 12 (MeSH) ; Chromosomes, Human, Pair 2 (MeSH) ; Chromosomes, Human, Pair 3 (MeSH) ; Chromosomes, Human, Pair 5 (MeSH) ; European Continental Ancestry Group: genetics (MeSH) ; European Continental Ancestry Group: statistics & numerical data (MeSH) ; Frizzled Receptors: genetics (MeSH) ; Genetic Predisposition to Disease: epidemiology (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Risk Factors (MeSH) ; Wnt Proteins: genetics (MeSH) ; Wnt Signaling Pathway: physiology (MeSH) ; Wnt3 Protein: genetics (MeSH) ; FZD10 protein, human ; Frizzled Receptors ; WNT10A protein, human ; WNT3 protein, human ; WNT6 protein, human ; Wnt Proteins ; Wnt3 Protein ; CYP27A1 protein, human ; Cholestanetriol 26-Monooxygenase

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Contributing Institute(s):

1. Implementation Science & Person-Centered Dementia Care (AG Roes)
2. Genomische Mathematik in der Neuroepidemiologie (GenomMathematik)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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