A Weighted Genetic Risk Score Predicts Surgical Recurrence Independent of High-Risk Clinical Features in Dupuytren’s Disease

BACKGROUND: Dupuytren’s disease is a very common, highly heritable palmar fibromatosis. In a recent genome-wide association study, 26 single-nucleotide polymorphisms were found to be associated with development of Dupuytren’s disease. The authors generated a weighted genetic risk score based on the genotype at these single-nucleotide polymorphisms. In two independent cohorts, they tested the association among high weighted genetic risk score, clinical features that predict a high risk of recurrence, and recurrence after surgery. METHODS: Clinical data were obtained from patient questionnaires and clinical records, with missing data accounted for by imputation. Genotyping was performed as part of the recent genome-wide association study. Logistic regression was performed to study the association among weighted genetic risk score, high-risk clinical features, and recurrence, with a weighted genetic risk score analyzed as a continuous variable, and also grouped into four categories. RESULTS: Using univariable logistic regression, a high weighted genetic risk score was associated with the presence of all high-risk clinical features: early age of onset, bilateral disease, ectopic disease, and a positive family history (p ≤ 0.004). After multivariable logistic regression accounting for these factors, an increased weighted genetic risk score was still associated with the need for repeated Dupuytren’s disease surgery (p = 0.004). CONCLUSIONS: The authors’ results suggest that a weighted genetic risk score is useful in predicting the risk of disease recurrence, and may be used by surgeons to personalize prognostication. In the future, a weighted genetic risk score may be useful for determining the most appropriate initial surgical procedure in patients with Dupuytren’s disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.