Genetic origin of Dupuytren’s disease and associated fibromatosis

The aetiology of Dupuytren’s disease (DD) has still not been fully elucidated. A genetic influence on its development has been suggested. The aim of this thesis was to investigate the genetic background of DD and its associated fibromatosis. This knowledge may lead to a better understanding of the disease and alternative treatments.

After studying the mode of inheritance of familial DD, we carried out a genome-wide association study to identify common genetic variants. The study yielded genome-wide significant associations at nine different loci and found genes in the Wnt-signaling pathway, suggesting that abnormalities in this pathway are key to the process of fibromatosis in DD.

We then examined if the nine DD susceptibility loci were also involved in Peyronie’s Disease (PD). We found a significant association at one of the DD susceptibility loci (WNT2 locus), thus providing evidence that PD and DD share genetic susceptibility factors. Finally, based on the nine SNPs, we found that patients with certain DD diathesis features were likely to have a higher risk score.

This research is a major leap forward in understanding the genetics of DD, but many questions about its origin still remain.