Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research

Abstract

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Keywords: Parkinson's disease; biobank; common genetic variation; genetic diversity; genome-wide association study.

Figure 1

Overall flow chart describing the details of the Lux-GIANT consortium. The consortium follows the “hub-spoke” model. The Lux-GIANT has established three main cores: genomics, clinical, and functional genomics. The University of Tubingen is the coordinator site. Luxembourg site aims to strengthen functional genomics and system biology. Functional core from India, National Brain Research Center, will be responsible for developing and maintaining iPSCs. Four main clinical-nodes capturing most of India are formed. These four nodes are connected to clinical sub-centers which span throughout India. The “central clinical node” aims to streamline the administrative process, which is required for clearance and sample shipment. The different nodes within India are connected with the main “central clinical node” for continuous update of cohort and members.

Figure 2

Clinical, genomics, bioinformatics, and functional cores in the Lux-GIANT consortium.

Figure 3

The PCA plot using the phase 3 1,000 Genomes Project showing the distribution of the South Asian population among the worldwide populations (left), and sub-populations from different regions of the Indian subcontinent (right).

Figure 4

Data management and access workflows in the Lux-GIANT network.