These markers may prove useful in predicting disease progression or recurrence.

Introduction 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. Aim 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). Main Outcome Measure 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.

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Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren´s disease, much of the inherited risk in Dupuytren´s disease still needs to be discovered. The already identified loci jointly explain ~1% of the heritability in this disease. To further elucidate the genetic basis of Dupuytren´s disease, we performed a genome-wide meta-analysis combining three genome-wide association study (GWAS) data sets, comprising 1,580 cases and 4,480 controls. We corroborated all nine previously identified loci, six of these with genome-wide significance (p-value < 5x10-8). In addition, we identified 14 new suggestive loci (p-value < 10−5). Intriguingly, several of these new loci contain genes associated with Wnt signalling and therefore represent excellent candidates for replication. Next, we compared whole-transcriptome data between patient- and control-derived tissue samples and found the Wnt/β-catenin pathway to be the top deregulated pathway in patient samples. We then conducted network and pathway analyses in order to identify protein networks that are enriched for genes highlighted in the GWAS meta-analysis and expression data sets. We found further evidence that the Wnt signalling pathways in conjunction with other pathways may play a critical role in Dupuytren´s disease.

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