Exploratory analysis of the genetics of impulse control disorders in Parkinson's disease using genetic risk scores

Objective: To study the association between impulse control disorders (ICDs) in Parkinson's disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits). Background: In absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD. Methods: We searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson's Progression Markers Initiative database (N = 368, 33% female, age range = [33-84]) and the Drug Interaction With Genes in Parkinson's Disease study (N = 373, 40% female, age range = [29-85]). Results: We considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis. Conclusion: Albeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.

Automated summary

This study aimed to investigate the genetic risk factors associated with impulse control disorders in Parkinson's disease by analyzing genetic risk scores for various known or putative risk factors. However, after testing in two large PD cohorts and conducting a meta-analysis, no significant associations were found. Despite the lack of success, this approach may prove useful in future studies as genotypic data becomes more available.