Gene Polymorphisms of Parkinson’s Disease Risk Locus and Idiopathic REM Sleep Behavior Disorder

<b>Background/Objectives</b>: Genetic factors play an important role in idiopathic rapid eye movement sleep behavior disorder (iRBD) but have not been fully studied. This study aimed to analyze the Parkinson's disease (PD)-related genetic loci in iRBD in the southern Chinese population. <b>Methods</b>: In this study, we recruited 292 individuals with PD, 62 with iRBD, and 189 healthy controls (HC). Candidate genes were identified primarily from the Parkinson's Progression Markers Initiative (PPMI) database. Genotypic and allele frequency analyses were conducted to compare the distribution across HC, iRBD, and PD groups. The effects of significant single-nucleotide polymorphisms (SNPs) on gene expression were examined. Clinical manifestations associated with different genotypes were also analyzed. The receiver operating characteristic (ROC) curve and Kaplan-Meier plots were utilized to further verify the diagnostic and predictive value of these SNPs. <b>Results</b>: We identified two significant SNPs associated with iRBD: rs13294100 of <i>SH3GL2</i> and rs165599 of <i>COMT</i>. Clinical scale and polysomnography data analysis indicated that iRBD patients with the GA or AA genotype at the <i>COMT</i> rs165599 locus have lower RBDSQ scores and higher sleep efficiency. Moreover, we identified that <i>COMT</i> rs165599 and <i>MCCC1</i> rs12637471 may play an important role in both PD and iRBD, while <i>SNCA</i> rs356181 was different between iRBD and PD. <b>Conclusions</b>: Our research revealed that in the southern Chinese demographic, genetic loci in <i>SH3GL2</i> and <i>COMT</i> were linked to iRBD and may act as potential biomarkers for iRBD risk. Additionally, there is evidence suggesting a partial genetic overlap between iRBD and PD, indicating a shared genetic predisposition.