Polygenic risk associations with clinical characteristics and recurrence of Dupuytren’s disease

Background
Dupuytren’s disease (DD) is a common complex trait, with varying presentation and severity, and incompletely understood etiology. Genome-wide association studies (GWAS) have identified several risk loci. Here, we examine whether genetic risk profiles generated from the latest DD GWAS are associated with clinical variation and disease severity as well as with genetic risk profiles of genetically correlated traits, including body mass index (BMI), triglycerides (TG), high-density lipoproteins (HDL), type 2 diabetes mellitus (T2D), and endophenotypes fasting glucose (FG), and glycated haemoglobin (HbA1c). Understanding the contribution of genetic variants to patient characteristics and DD recurrence is a necessary step toward accurate prognostication of this highly heritable disease.

Methods
We used a well-characterized cohort of 1,461 DD patients with available phenotypic and genetic data. Phenotype data include age of onset, recurrence, and family history of disease. Polygenic risk scores (PRSs) of DD, BMI, TG, HDL, T2D, FG, and HbA1c using various significance thresholds were calculated with PRSice using the most recent GWAS summary statistics. Control data from Lifelines were used to determine p-value cut-offs for PRS generation explaining most variance. 

Results
The optimal PRS for DD was significantly associated with a positive family history for DD, age of onset, disease onset before the age of 50, and recurrence. We found a significant correlation between the PRSs for DD and BMI. 

Conclusions
The genetic risk profile for DD also explains part of the clinical variation and disease severity of DD. It may therefore aid in choosing initial treatment and in personalized medicine in future.

Key words: Dupuytren’s disease, Dupuytren’s contracture, Dupuytren’s diathesis, genetic risk, polygenic risk score, GWAS.