Polygenic Risk Associations with Clinical Characteristics and Recurrence of Dupuytren Disease

Background: Dupuytren disease (DD) is a common complex trait, with varying severity and incompletely understood cause. Genome-wide association studies (GWAS) have identified risk loci. In this article, we examine whether genetic risk profiles of DD in patients are associated with clinical variation and disease severity and with patient genetic risk profiles of genetically correlated traits, including body mass index (BMI), triglycerides, high-density lipoproteins, type 2 diabetes mellitus, and endophenotypes fasting glucose and glycated hemoglobin. Methods: The authors used a well-characterized cohort of 1461 DD patients with available phenotypic and genetic data. Phenotype data include age at onset, recurrence, and family history of disease. Polygenic risk scores (PRSs) of DD, BMI, triglycerides, high-density lipoprotein, type 2 diabetes, fasting glucose, and hemoglobin A1c 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 cutoffs for PRS generation explaining most variance. Results: The PRS for DD was significantly associated with a positive family history for DD, age at onset, disease onset before the age of 50, and recurrence. We also found a significant negative correlation between the PRSs for DD and BMI. Conclusions: Although GWAS studies of DD are designed to identify genetic risk factors distinguishing case/control status, we show that the genetic risk profile for DD also explains part of its clinical variation and disease severity. The PRS may therefore aid in accurate prognostication, choosing initial treatment and in personalized medicine in the future. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.