Whole-genome sequencing of 197 cases with Parkinson’s disease reveals novel pathogenic variants in the Indian population

AI Summary

Whole-genome sequencing of 197 Indian PD cases identified pathogenic variants in seven PD-associated genes, with diagnostic rates 27.6% in EOPD and 2.2% in LOPD.
Seven variants novel to Indian populations highlight unique genomic diversity and frequent mutations in GBA1 and PRKN.
Patients showed significant enrichment of lysosomal pathway variants and higher polygenic risk scores, supporting a combined monogenic and polygenic PD architecture.

NPJ Parkinsons Dis. 2026 Jul 6. doi: 10.1038/s41531-026-01462-0. Online ahead of print.

ABSTRACT

Most insights into the genetics of Parkinson’s disease (PD) arise from European cohorts, leaving the genomic diversity of India underexplored. To address this gap, we performed whole-genome sequencing of 197 Indian PD cases (106 with early-onset PD (EOPD) and 91 with late-onset PD (LOPD)), capturing SNVs, indels, splice, and structural variants. We identified pathogenic variants in 31 cases across seven PD-associated genes (GBA1, PRKN, PINK1, DJ1, SYNJ1, SNCA, and PLA2G6), giving a diagnostic rate of 27.6% in EOPD and 2.2% in LOPD. Seven of these variants were novel to Indian populations. GBA1 and PRKN were the most frequently mutated genes. Candidate genes with pathogenic variants were enriched in lysosomal pathways. Cases had significantly higher polygenic risk scores, supporting a polygenic contribution to PD risk. Our study establishes one of the first comprehensive sequencing-based resources for PD genetics in India, and underscores the need for large-scale genomic studies across diverse populations.

PMID:42409815 | DOI:10.1038/s41531-026-01462-0

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