Rapid motor progression of Parkinson's disease associates with clinical and genetic variants.

Ling-Xiao Cao,Ying-Shan Piao,Yong Jiang,Yue Huang

doi:10.52586/5044

Abstract

Parkinson's disease (PD) is caused by the interplay of genetic and environmental factors during brain aging. About 90 single nucleotide polymorphisms (SNPs) have been recently discovered associations with PD, but whether they associate with the clinical features of PD have not been fully addressed yet. Clinical data of 365 patients with PD who enrolled in Parkinson's Progression Markers Initiative (PPMI) study were obtained. Patients with rapid motor progression were determined through clinical assessments over five years follow-up. In addition, genetic information of 44 targeted SNPs was extracted from the genetic database of NeuroX for the same cohort. Logistic regression was used to analyze the genetic associations with rapid motor progression of PD. Among 365 patients with PD, there are more male (66%) than female (34%). Seven SNPs (rs6808178, rs115185635, rs12497850, rs34311866, rs3793947, rs11060180, rs9568188) were associated with faster motor progression (p < 0.05), and only rs6808178 passed multiple comparison correction (p < 0.0011). In addition, the extended 44 SNPs with autonomic dysfunction reach a fair prediction of AUC at 0.821. Genetics and autonomic function factors contribute to the motor progression at the clinical initiation of PD.

Highlights

Parkinson disease (PD) is the second most common neurodegenerative disorder in the elderly, which is characterized by motor disabilities such as tremor, bradykinesia, rigidity as well as non-motor symptoms including autonomic dysfunction, hyposmia, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and other clinical features [1, 2]
Baseline autonomic dysfunction was associated with rapid motor progression (OR = 1.042, p = 0.039), while other non-motor symptoms at baseline were not (Table 2)
We found that among the non-motor symptoms, early and severe autonomic dysfunction was associated with rapid motor progression, which is consistent with previous research [37]

Summary

Introduction

Parkinson disease (PD) is the second most common neurodegenerative disorder in the elderly, which is characterized by motor disabilities such as tremor, bradykinesia, rigidity as well as non-motor symptoms including autonomic dysfunction, hyposmia, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and other clinical features [1, 2]. PD susceptibility genes have been associated with PD clinical features, such as onset age, subtype, and progression of PD [14,15,16,17,18,19,20,21,22,23] These studies were either based on cross-sectional PD cohorts or with limited genetic variants involved. This study aims based on recent GWAS identified PD risk SNPs to investigate genetic and clinical associations with rapid motor progression in a longitudinal PD cohort with five-year follow up [10, 11]

Objectives

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Results

Conclusion