Objective: Our aims were to estimate ICD heritability and to predict incident ICD behaviour by a candidate genetic multivariable panel in PD patients.

Background: Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in Parkinson’s disease (PD) patients. Genetic susceptibility has been shown to contribute to ICD in the general population.

Methods: Data from de novo PD patients, drug-naïve, and free of ICD behaviour at baseline were obtained from the Parkinson’s Progression Markers Initiative cohort. Incident ICD behaviour was defined as a positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP). ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. Thirteen candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1, and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves.

Results: Among 276 PD patients included in the analysis, 86% started DRT, 40% dopamine agonists (DA), and 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95%CI [70-83%]) compared to prediction based on clinical variables only (AUC=65%, 95%CI [58-73%], p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95%CI [80-93%]). OPRK1, HTR2A, and DDC genotypes were the strongest genetic predictive factors.

Conclusions: Our results show that adding a candidate genetic panel increases ICD predictability in PD, suggesting potential for developing clinical-genetic models to identify those patients at highest risk of ICD development which can guide DRT prescribing in this population.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/predicting-incident-impulse-control-disorder-behaviour-in-parkinsons-disease-patients-using-a-clinical-genetic-model/