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Funded Studies

Deciphering the Genetic Architecture of the LRRK2 Gene in the Indian Population

Genetic variability in the LRRK2 gene is recognized as one of the most common cause of Parkinson’s disease (PD) mainly in the Caucasian, African-Arab, Ashkenazi Jewish and East Asian populations. There is a complete lack of knowledge regarding the role of LRRK2-dependent PD in the Indian population. To understand the role of the LRRK2 locus and its prevalence in the Indian population, a systematic unbiased assessment of the LRRK2 locus (location on a chromosome) will be performed in Indian population. This study will address if genetic variants identified mainly in the Caucasian and other ethnically diverse populations confer risk to the Indian population, and, conversely, if genetic variants identified in the Indian population confer susceptibility to other ethnically diverse populations.

Project Description:
Targeted re-sequencing of the LRRK2 locus will be performed in 700 Parkinson’s patients and 400 matched controls ascertained from India. Using standard bioinformatic analytical tools, putative variants will be selected for further validation in the Genetic Epidemiology of Parkinson’s Disease (GEOPD) cohort.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project will define the clinical relevance of the LRRK2 gene in the Indian population. The identification of novel, putative risk variants will be subsequently used for functional characterization to define the molecular mechanisms of neurodegeneration in PD and develop disease-modifying therapies for PD.

Anticipated Outcome:
This study, for the first time, will provide a comprehensive catalogue of genetic variants for the LRRK2 gene for PD from the Indian subcontinent population. This cataloging of minor allele frequency of variants will play an important role in determining the clinical relevance of the LRRK2 gene in the Indian population. 


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