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

J Invest Dermatol. 2013 Jun;133(6):1489-96. doi: 10.1038/jid.2013.43. Epub 2013 Jan 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alopecia / epidemiology*
  • Alopecia / etiology
  • Alopecia / genetics*
  • Alopecia / metabolism
  • Cholestanetriol 26-Monooxygenase / genetics
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 5
  • 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
  • White People / genetics
  • White People / statistics & numerical data
  • Wnt Proteins / genetics*
  • Wnt Signaling Pathway / physiology*
  • Wnt3 Protein / genetics

Substances

  • FZD10 protein, human
  • Frizzled Receptors
  • WNT10A protein, human
  • WNT3 protein, human
  • WNT6 protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase