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

Abstract

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. 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. 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). 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. Risk, III.