BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease

Abstract

AbstractBackgroundA multitude of genetic variants confer a risk of Parkinson’s disease (PD), however, whether these risk variants affected the motor symptoms of PD patients remain largely elusive. The objective of this study is to investigate the effects ofBCKDKrs14235 (G > A), a risk variant associated with PD risk, on the motor manifestations and brain networks of PD patients.MethodsPD patients (n = 146) receiving magnetic resonance imaging from Parkinson’s Progression Markers Initiative (PPMI) database were investigated. The effects ofBCKDKrs14235 on the motor manifestations and brain networks of PD patients were systematically evaluated.ResultsBCKDKrs14235 A allele was associated with milder motor symptoms in PD patients.BCKDKrs14235 significantly modified the topology of brain structural and functional network. The assortativity in structural network was negatively associated with rigidity in PD while the shortest path length of right pallidum was positively associated with Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) scores. The mediation analysis suggested that assortativity in structural network mediated the effects ofBCKDKrs14235 on rigidity and the shortest path length of right pallidum mediated the effects ofBCKDKrs14235 on UPDRS-III scores.ConclusionsBCKDKrs14235 significantly shaped the motor impairment and network topology of PD patients. Differential network metrics mediated the effects ofBCKDKrs14235 on rigidity and UPDRS-III scores of PD patients. Future studies were required to identify the molecular mechanisms underlying the effects ofBCKDKrs14235 on motor impairment and brain network metrics of PD patients.