Author:
Chen Zhichun,Wu Bin,Li Guanglu,Zhou Liche,Zhang Lina,Liu Jun
Abstract
AbstractOver 90 genetic variants have been found to be associated with Parkinson’s disease (PD) in genome-wide association studies, however, the neural mechanisms of these identified genetic variants conferring risk of PD were largely unexplored. The objective of this study was to identify essential genetic variants in PD for future functional and mechanistic studies. We revealed 14 single nucleotide polymorphisms (SNPs) conferring risk of PD were significantly correlated with brain gene expressions. Although they were not significantly associated with the clinical presentations of PD patients in multivariate regression models, multi-SNP models constructed by several genetic variants powerfully predicted clinical presentations of PD patients. Among 14 SNPs,GPNMBrs199347 significantly modified the activity of sensorimotor network (adjustedp< 0.0007, FDR corrected) after adjusting age, sex, disease duration, and the genotypes of remaining 13 SNPs. Graph-based network analysis further demonstrated thatGPNMBrs199347 had remarkable effects on the global topology of functional network and specifically shaped the nodal network metrics of bilateral caudate.GPNMBrs199347 was not associated with significant changes of structural network metrics. Our findings support thatGPNMBrs199347 is an essential genetic variant specifically shaping functional network of PD patients.
Publisher
Cold Spring Harbor Laboratory