Plast Reconstr Surg. 2023 May 31. doi: 10.1097/PRS.0000000000010775. Online ahead of print.
ABSTRACT
BACKGROUND: Dupuytren’s disease (DD) is a common complex trait, with varying severity and incompletely understood etiology. Genome-wide association studies (GWAS) have identified risk loci. Here, we examine whether genetic risk profiles of DD in patients are associated with clinical variation and disease severity as well as with patient 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 hemoglobin (HbA1c).
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 PRSs generation explaining most variance.
RESULTS: The 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 also found a significant negative correlation between the PRSs for DD and BMI.
CONCLUSIONS: While 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 future.
PMID:37257093 | DOI:10.1097/PRS.0000000000010775
