Gene4PD: A Comprehensive Genetic Database of Parkinson's Disease

Bin Li; Guihu Zhao; Qiao Zhou; Yali Xie; Zheng Wang; Zhenghuan Fang; Bin Lu; Lixia Qin; Yuwen Zhao; Rui Zhang; Li Jiang; Hongxu Pan; Yan He; Xiaomeng Wang; Tengfei Luo; Yi Zhang; Yijing Wang; Qian Chen; Zhenhua Liu; Jifeng Guo; Beisha Tang; Jinchen Li

doi:10.3389/fnins.2021.679568

Gene4PD: A Comprehensive Genetic Database of Parkinson's Disease

Front Neurosci. 2021 Apr 26:15:679568. doi: 10.3389/fnins.2021.679568. eCollection 2021.

Authors

Bin Li^{1

2

3}, Guihu Zhao^{1

2}, Qiao Zhou¹, Yali Xie¹, Zheng Wang¹, Zhenghuan Fang⁴, Bin Lu⁵, Lixia Qin², Yuwen Zhao², Rui Zhang², Li Jiang², Hongxu Pan², Yan He², Xiaomeng Wang⁴, Tengfei Luo⁴, Yi Zhang¹, Yijing Wang⁴, Qian Chen¹, Zhenhua Liu², Jifeng Guo², Beisha Tang^{1

2}, Jinchen Li^{1

2

4}

Affiliations

¹ National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
³ Mobile Health Ministry of Education-China Mobile Joint Laboratory, Xiangya Hospital, Central South University, Changsha, China.
⁴ Center for Medical Genetics, Hunan Key Laboratory, School of Life Sciences, Central South University, Changsha, China.
⁵ Department of Pathogen Biology, School of Basic Medical Sciences, Central South University, Changsha, China.

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30-50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD. In conclusion, Gene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.

Keywords: Gene4PD database; PD-associated genes; Parkinson’s disease; age at onset; genetic variant.