Objective: To examine the relationship between a polygenic risk score (GRS) associated with Parkinson’s disease (PD) and impulse control disorders (ICDs) in PD.

Background: Genome wide association studies (GWAS) have brought forth a GRS associated with increased risk of PD and younger disease onset. Impulse control disorders (ICDs) are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. There are few known susceptibility genes for ICDs, and it is unknown whether ICDs and PD share genetic susceptibility.

Method: We used data from a multicentre longitudinal cohort of consecutive PD patients with less than 5 years of disease duration at baseline followed annually up to 6 years (DIG-PD). At each visit, symptoms of dopaminergic dysregulation in different activities were evaluated by movement disorders specialists during face-to-face semistructured interviews. ICDs are defined by a diagnosis of compulsive gambling, buying, eating, or sexual behavior. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted GRS based on 41 SNPs associated with PD [1]. We estimated the association between GRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for time since baseline, age and disease duration at baseline, sex, marital status, education level, use of dopamine agonists (DA) and levodopa. Analyses were performed overall and restricted to DA users.

Results: Of 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p<0.001) as well as higher GRS values (p=0.06). At baseline, there was no association between the GRS and ICDs (overall, p=0.13; DA users, p=0.83). The prevalence of ICDs increased over time similarly in the quartiles of the GRS (overall, p=0.23; DA users, p=0.71).

Conclusion: Our findings are not in favor of common susceptibility genes for PD and ICDs. Additional studies are needed to understand the genetic factors and mechanisms leading to ICDs in PD.

References: [1] Chang D, Nalls MA, Hallgrimsdottir IB, et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet 2017;49:1511-1516

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-polygenic-risk-score-is-not-associated-with-impulse-control-disorders-a-longitudinal-study/