BIN3 rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson's disease

BackgroundExcessive daytime sleepiness (EDS) is one of the most common non-motor symptoms in Parkinsons disease (PD). Previous studies showed that PD patients with EDS exhibited more severe motor and non-motor symptoms. Our recent studies revealed that BIN3 rs2280104 was negatively associated with scores of Epworth Sleepiness Scale (ESS) in PD patients. The objective of this study is to examine whether BIN3 rs2280104 shapes brain networks of PD patients and whether network metrics associated with BIN3 rs2280104 mediate the effects of BIN3 rs2280104 on EDS. MethodsPD patients (n = 144) receiving functional magnetic resonance imaging in Parkinsons Progression Markers Initiative (PPMI) database were investigated. The clinical manifestations and graphical metrics of structural and functional network were compared among different genotype groups of BIN3 rs2280104. The mediation analysis was used to explore the causal associations between network metrics modified by BIN3 rs2280104 and EDS of PD patients. ResultsESS scores were associated with more severe motor and non-motor symptoms. BIN3 rs2280104 T allele was negatively associated with ESS scores in PD patients. Additionally, BIN3 rs2280104 significantly shaped structural and functional network metrics of PD patients. The nodal Cp of left superior temporal pole in functional network and the degree centrality of left calcarine in structural network were negatively associated with ESS scores, however, only the degree centrality of left calcarine in structural network mediated the effects of BIN3 rs2280104 on EDS of PD patients. ConclusionsTo summarize, BIN3 rs2280104 is significantly associated with EDS and network topology of PD patients. Additionally, the degree centrality of left calcarine in structural network mediated the effects of BIN3 rs2280104 on EDS. Future studies were required to identify the molecular mechanisms underlying the effects of BIN3 rs2280104 on EDS and brain network metrics of PD patients.