Peter Lichntner

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Sabbir Ansari

National Institute of Cholera and Enteric Diseases

Dan Vitale

Data Tecnica International (United States)

Cornelis Blauwendraat

National Institutes of Health

Brian Fiske

Michael J. Fox Foundation

Pettarusp M. Wadia

Jaslok Hospital

Sindhuja Mohareer

Niraj Kumar

All India Institute of Medical Sciences

Ashwin Ashok Kumar Sreelatha

University of Tübingen

Kuldeep Shetty

Narayana Health

Roopa Rajan

All India Institute of Medical Sciences

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Sree Chitra Thirunal Institute for Medical Sciences and Technology

All India Institute of Medical Sciences

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All India Institute of Medical Sciences Bhopal

All India Institute of Medical Sciences Raipur

John Wiley & Sons (United States)

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National Institute of Mental Health and Neurosciences

National Institute on Aging

National Institutes of Health

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Deciphering the Genetic Architecture of Parkinsons Disease in India

medRxiv (Cold Spring Harbor Laboratory) (2025)

Asha Kishore Ashwin Ashok Kumar Sreelatha Amabel Tenghe Rupam Borgohain Divya Kalikavil Puthanveedu

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.

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10.1101/2025.02.17.25322132

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