Dataset Information

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

ABSTRACT: Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD.Data from de novo patients with PD, 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 positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 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.Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 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% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors.Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management.

SUBMITTER: Kraemmer J

PROVIDER: S-EPMC5098340 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

Kraemmer Julia J Smith Kara K Weintraub Daniel D Guillemot Vincent V Nalls Mike A MA Cormier-Dequaire Florence F Moszer Ivan I Brice Alexis A Singleton Andrew B AB Corvol Jean-Christophe JC

Journal of neurology, neurosurgery, and psychiatry 20160413 10

<h4>Objectives</h4>Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD.<h4>Methods</h4>Data from de novo patients with PD, 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 pos ...[more]

PMID: 27076492

Similar Datasets

Project description:Introduction:Impulse control disorders (ICDs) are frequent non-motor symptoms in Parkinson's disease (PD), with potential negative effects on the quality of life and social functioning. ICDs are closely associated with dopaminergic therapy, and genetic polymorphisms in several neurotransmitter pathways may increase the risk of addictive behaviors in PD. However, clinical differentiation between patients at risk and patients without risk of ICDs is still troublesome. The aim of this study was to investigate if genetic polymorphisms across several neurotransmitter pathways were associated with ICD status in patients with PD. Methods:Whole-exome sequencing data were available for 119 eligible PD patients from the Norwegian ParkWest study. All participants underwent comprehensive neurological, neuropsychiatric, and neuropsychological assessments. ICDs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Single-nucleotide polymorphisms (SNPs) from 17 genes were subjected to regression with elastic net penalization to identify candidate variants associated with ICDs. The area under the curve of receiver-operating characteristic curves was used to evaluate the level of ICD prediction. Results:Among the 119 patients with PD included in the analysis, 29% met the criteria for ICD and 63% were using dopamine agonists (DAs). Eleven SNPs were associated with ICDs, and the four SNPs with the most robust performance significantly increased ICD predictability (AUC?=?0.81, 95% CI 0.73-0.90) compared to clinical data alone (DA use and age; AUC?=?0.65, 95% CI 0.59-0.78). The strongest predictive factors were rs5326 in DRD1, which was associated with increased odds of ICDs, and rs702764 in OPRK1, which was associated with decreased odds of ICDs. Conclusion:Using an advanced statistical approach, we identified SNPs in nine genes, including a novel polymorphism in DRD1, with potential application for the identification of PD patients at risk for ICDs.

Dataset Information

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

Publications

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure