Large Indian Genome wide study identifies key genes for Parkinson disease in young people, uncovers South Asia specific mutation

Bengaluru, February 07, 2023: A new study conducted by MedGenome, a leading global genomics company in South Asia, together with Parkinson’s Research Alliance of India (PRAI) found that rare genetic variations along with common variants derived through polygenic risk score (PRS) can detect Young Onset of Parkinson’s Disease (YOPD). A pilot study was published through this collaboration in the 2022 July edition of the Advanced Biology journal with 100 whole genome of Parkinson’s Disease patients [1]. The new study validated the existing knowledge along with new findings on the genetics of Parkinson’s disease which got published in the prestigious journal, Movement Disorders.

This is a first of a kind study conducted in India aimed to initiate a population-based genetic analysis of Young Onset Parkinson’s disease (YOPD) in Indian population. The Genetics of PAN-India Young Onset Parkinson Disease (GOPI-YOPD), a multicentre Pan India project- recruited 1000 patients through a network of 10 specialty Movement Disorder Centers/Neurology clinics across India.

The research paper investigates genetic variations associated with young-onset Parkinson’s disease (YOPD) in the Indian population. The study validates existing findings from European populations and identifies major genetic mutations in genes such as PRKN (13%), GBA, PINK1, and LRRK2 with a notable discovery of rare South Asia specific mutation in the GBA gene, including p.Ser164Arg, confirmed through experimental research. This mutation is not seen in other populations. The study aggregates the common genetic variations into a polygenic risk score (PD-PRS), introducing a genetic screening test for assessing the risk of developing Parkinson’s disease. This comprehensive analysis of rare and common genetic variations in YOPD in the Indian population enhances the understanding of the genetic basis of Parkinson’s disease and introduces a novel genetic screening approach to assess disease risk. This opens door for a first ever genetic screening in India for Parkinson’s Disease in high-risk individuals and affected families. The results can be evaluated by clinicians and geneticists to guide patients in early intervention, disease risk mitigation, and better treatment strategies.

The genomic analysis for the study was done at MedGenome Labs using MedGenome’s SARGAM array (South Asian Research Genotyping Array for Medicine), which has curated content from a proprietary database of 2.5 million variants unique to the South Asian population which is not available in any publicly available genetic database.

Prof Rupam Borgohain, Secretary of Parkinson’s Research Alliance of India (PRAI) and Chairman, PDMDRC, Citi Neuro Centre, Hyderabad said, “Parkinson’s disease is a common neurological disorder causing tremors, slowness of movements, stiffness and walking difficulties in most. It is caused by a complex interaction between external environmental and familial or genetic factors. Based on the initiative of Dr Prashanth LK, Specialist in Movement disorders, Parkinsons disease and Movement disorders clinic, Bengaluru, a first of its kind- India wide registry of Young Onset Parkinson’s Disease (disease starting at age less than 50 years) was started by PRAI and resulted in insights into clinical and genetic aspects of Indian patients. Parkinson’s disease with onset less than 20 years (juvenile PD), 20-40 years (young onset PD) and 40-50 years (early onset PD) have different clinical features. The role of genetic factors seems to be higher in these patients compared to older age and this collaborative project of PRAI with MedGenome has identified unique genetic fingerprints in Indian patients.”

Dr Vedam Ramprasad, CEO, MedGenome said, “MedGenome has always been at the forefront of equipping clinicians and patients with the latest and most innovative tools in healthcare by leveraging the power of genomics. With the increased focus on personalised medicine, using risk screening tools such as Polygenic Risk Score (PRS) will enable us to predict an individual’s genetic liability to rare and inherited diseases much in advance before the symptoms start appearing. With these findings, we aim to offer a prognostic value to clinicians while catering to the need of a systematic genetic evaluations for timely prevention and management of several diseases.”

Parkinson’s disease is the second most common neurodegenerative disorder in adults in the age bracket of 60 years and above. The Global Burden of Disease Study (2018) states that the burden of Parkinson’s disease has doubled across the globe over the past two decades. India accounts for approximately 10% of the global burden, which translates to nearly 0.58 million patients living with the disease.