Genetics of Parkinson's Disease: Contributions from India

Unveiling the aetiology of Parkinson’s disease (PD) has come a long way from the early belief on PD being caused by exogenous and endogenous toxins, 1 , 2 to gene-environment interactions, 3 to a probable role of a single gene and combinations thereof. 4 It has also moved subsequently from the hypothesis based candidate gene testing approach to hypothesis free genome-wide association studies (GWAS) and recently to next generation sequencing tools (NGS) for rare variant identification. Indeed, it may not be an exaggeration to say that discovery genomics stepped into a golden era between the end of the last and beginning of this century. Concomitant progress in functional genomics and systems biology approaches are providing some insights into the etiological mechanisms underlying diseases with promising leads for new therapeutics. This overview attempts to capture some of the excitement in contemporary medical genomics with specific reference to PD genetics which has witnessed notable progress and with particular focus on the novel findings in the ethnically and genetically distinct Indian population. Recent advances in the country including: i) putative causal gene discoveries, consequent recognition of newer pathways underlying disease biology, iii) shared and unique mutation spectra across ethnic groups, iv) implications of these findings for predictive medicine, and v) the most recent excitement with induced pluripotent stem cells (iPSCs) combined with genome editing technology for in vitro disease modelling and personalized medicine are presented in brief.