Deciphering the Genetic Architecture of Parkinsons Disease in India

The genomic landscape of the Indian population, particularly for age-related disorders like Parkinsons disease (PD) remains underrepresented in global research. Genetic variability in PD has been studied predominantly in European populations, offering limited insights into its role within the Indian population. To address this gap, we conducted the first pan-India genomic survey of PD involving 4,806 cases and 6,364 controls, complemented by a meta-analysis integrating summary statistics from a multi-ancestry PD meta-analysis (N=611,485). We further leveraged RNA-sequencing data from lymphoblastoid cell lines of 731 individuals from the 1000 Genomes project to evaluate the expression of key loci across global populations. Our findings reveal a higher genetic burden of PD in the Indian population compared to Europeans, accounting for [~]30% of the previously unexplained heritability. Thirteen genome-wide significant loci were identified, including two novel loci, with an additional three loci uncovered through meta-analysis. Polygenic risk score analysis showed moderate transferability from European populations. Our results highlight the importance of genetic loci in immune function, lipid metabolism and SNCA aggregation in PD pathogenesis, with gene expression variability emphasizing population-specific differences. We also established South Asias largest PD biobank, providing a foundation for patient-centric approaches to PD research and treatment in India.