title: WNT2 locus is involved in genetic susceptibility of Peyronie's disease.
abstract: BACKGROUND
  Peyronie's disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren's disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated with DD. Seven of these loci mapped within or near genes of the canonical WNT pathway and each locus yielded relatively large odds ratios (ORs) for DD disease status.
  
  
  OBJECTIVE
  Given the clinical overlap between PD and DD, we examined whether the nine DD susceptibility loci are also involved in PD.
  
  
  METHODS
  An association study was performed using a case/control design. From 2007 to 2010, we prospectively included 111 men who had been clinically diagnosed with PD. Control subjects (N = 490 males) were randomly drawn from a population-based cohort from the same region of the Netherlands. Allele frequencies in the 111 PD cases and 490 controls were compared using a 1-degree-of-freedom basic chi-square test. A P value < 0.05 after Bonferroni correction for the nine tested single nucleotide polymorphisms (SNPs) was considered statistically significant (i.e., P < 0.0056).
  
  
  METHODS
  Association of genetic markers (SNPs) with PD.
  
  
  RESULTS
  We observed significant association with SNP rs4730775 at the wingless-type MMTV integration site family member 2 (WNT2) locus on chromosome 7 (P = 0.0015, OR 0.61), but found no evidence for the other eight loci being involved with PD despite the large effect size seen for some of these variants in DD. The WNT2 association was even more significant after we removed 15 patients with comorbid DD.
  
  
  CONCLUSIONS
  WNT2 is a susceptibility locus for PD and our finding provides evidence for a partly shared genetic susceptibility between PD and DD.
authors.affiliation: Department of Plastic Surgery, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Guido H
authors.initials: GH
authors.lastname: Dolmans
authors.forename: Paul M
authors.initials: PM
authors.lastname: Werker
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.forename: Rien J
authors.initials: RJ
authors.lastname: Nijman
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D004387:Dupuytren Contracture / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010411:Penile Induration / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051154:Wnt2 Protein / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C495244:WNT2 protein, human; D051154:Wnt2 Protein