For decades, what we knew about the genetics of Parkinson’s disease came almost entirely from studies conducted in European populations. That knowledge was assumed to be universal. It isn’t. And India — with 1.48 billion people, over 4,500 ethnolinguistic groups, and a pattern of genetic diversity unlike anywhere else in the world — is finally beginning to generate the data that tells a different, more specific, and more useful story.
Why the Genetic Map Was Never Really Ours
Genome-wide association studies (GWAS) — large-scale analyses that scan the genome for variants associated with a disease — have identified more than 90 independent risk loci for Parkinson’s disease globally. But the overwhelming majority of those discoveries were made in people of European ancestry. Less than 1% of all GWAS ever conducted have included Indian participants. That is not a minor gap. It is a structural blind spot in one of the most consequential areas of neurological research.
The problem isn’t only about representation in a demographic sense. Allele frequencies — how common a particular genetic variant is in a population — differ significantly across ancestry groups. A variant that is rare in European populations might be common in an Indian subgroup, and vice versa. Linkage disequilibrium patterns (the way variants are inherited together) also differ. This means that genetic risk tools built on European data may simply not apply with the same accuracy to Indian patients. The risk scores don’t transfer cleanly. The findings don’t generalise the way they’ve often been assumed to.
India adds another layer of complexity: it is not genetically homogeneous. The Indian subcontinent is home to multiple major ancestry clades shaped by thousands of years of endogamy — marriage within communities — and relatively limited mixing between many of those groups. That means genetic variants can be enriched in specific communities, rare or absent in others, and the picture looks different depending on which part of the country a patient comes from. As we’ve discussed in the context of how chronic conditions interact with identity and community on Doctor Mentis, the social and the biological are rarely as separate as they appear.
What Parkinson’s Actually Is — And Why Genetics Matters Here
Parkinson’s disease is a progressive neurodegenerative condition caused by the loss of dopamine-producing neurons in a brain region called the substantia nigra. As those neurons decline, the characteristic motor symptoms emerge: tremor at rest, rigidity, slowness of movement (bradykinesia), and postural instability. But Parkinson’s is not purely a motor disorder. Anxiety, depression, sleep disturbances, cognitive changes, and autonomic dysfunction are well-documented non-motor features — as we’ve explored in our piece on sleep disorders in movement disorders, where disrupted nights compound the daytime burden considerably.
At the cellular level, a protein called alpha-synuclein misfolds and aggregates into structures called Lewy bodies, which accumulate in neurons and are considered a pathological hallmark of the disease. While most cases are sporadic — meaning no single inherited cause is identified — genetics shapes individual risk in important and increasingly decipherable ways.
India is estimated to have between 5.8 and 10 lakh people living with Parkinson’s disease, based on available national estimates, though precise figures are difficult to establish given gaps in diagnosis and documentation at a population level. What is clear is that as India’s population ages, the burden will grow — and without India-specific genetic data, clinicians and researchers will be working with tools that weren’t built for their patients.
The Variants That Tell a Different Story
Some of the most important early clues about how Indian Parkinson’s genetics differs from the European model come from specific genes that have been studied extensively in both populations.
LRRK2 is among the most studied Parkinson’s-related genes globally. The G2019S variant in LRRK2 — a significant risk mutation in some European and North African populations — is far less common in Indian PD cohorts. Indian studies instead implicate a different LRRK2 variant: rs11175666, identified in the 2025 pan-Indian GWAS preprint (medRxiv; peer review pending as of June 2026) at a position approximately 14 kilobases from the European-associated signal, with moderate linkage disequilibrium between the two. This isn’t a translation error — it’s a fundamentally different genetic signal in the same gene, which has real implications for how genetic testing is interpreted and what risk factors clinicians should be looking for.
GBA1, the gene encoding the enzyme glucocerebrosidase, is the most common genetic risk factor for Parkinson’s across multiple populations. In Indian cohorts, variants in GBA1 have shown associations with Parkinson’s risk, though the specific variant frequencies and effect sizes in Indian samples differ from those documented in European studies. The 2025 preprint (peer review pending) reports associations for GBA1 variants in this cohort, but precise odds ratio comparisons with European data should be interpreted cautiously until the work has been peer-reviewed.
PRKN (Parkin) is highly relevant in the Indian context specifically for early-onset Parkinson’s disease — cases diagnosed before age 50. In some Indian early-onset PD cohorts, GBA1 and PRKN together may account for roughly 15–20% of cases, though the exact proportion depends heavily on cohort selection and testing methodology; clinic-based cohorts enriched for familial cases will show higher yields than population-based samples. PRKN deletions — particularly homozygous deletions — have been among the more consistent findings in Indian genetic studies of young-onset disease.
SNCA, encoding alpha-synuclein, has shown genome-wide significant association with Parkinson’s in the Indian population across two separate studies, including the 2023 South Asian early-onset GWAS and the 2025 pan-Indian study. Notably, the lead SNP in the SNCA region colocalized strongly with the European GWAS signal — suggesting this is one of the more conserved findings across ancestry groups, which is itself informative.
The 2025 Pan-Indian GWAS: What It Found and What It Means
In February 2025, a team led by Asha Kishore and colleagues (Lux-GIANT collaboration) posted the largest Parkinson’s GWAS ever conducted in India to medRxiv (DOI: 10.1101/2025.02.17.25322132; preprint, peer review pending as of June 2026). The study recruited 4,806 cases and 6,364 controls over three years from a network of six hub centres and 14 sub-nodes spread across the country — a deliberately pan-Indian design that aimed to capture the country’s geographic and genetic breadth.
The study mapped common genetic associations with PD, identified novel putative loci, and confirmed the role of previously identified loci, while also conducting cross-population polygenic prediction analyses comparing Indian and European ancestry participants.
A note on language here that matters: any description of loci as “entirely novel globally” requires cross-referencing against the largest published PD meta-analyses (including Nalls et al. 2019 and subsequent releases). The preprint itself notes that the study’s primary limitation is the absence of an independent Indian replication cohort — something the team acknowledges directly and is working to address in a second recruitment phase. Until peer review is complete and replication data exist, the appropriate framing for novel loci is “not previously reported in major global meta-analyses” rather than claiming global novelty with certainty.
The consistent directionality of effect estimates for key loci, as observed in the European population and the meta-analysis, reduces the likelihood of spurious associations — which provides some reassurance about the robustness of the core findings even in the absence of a replication cohort.
The infrastructure built for this study — a well-characterised PD biobank spanning the country — may be as significant as any individual finding. It is the foundation that future Indian Parkinson’s research will build on.
GAP-India and the Bigger Architecture
Running in parallel with the GWAS work is GAP-India (Genetics and Parkinson’s — India), a longitudinal cohort initiative that aims to enrol 25,000 PD cases and 25,000 controls with deep phenotyping — detailed clinical characterisation alongside genetic data. The goal is not just to generate genetic association data, but to create the kind of richly annotated resource that allows researchers to ask questions about how genetics interacts with clinical trajectory, treatment response, and disease subtype in an Indian population.
Geographical locations of the enrolling sites were chosen to consider India’s unique population structure and to enable a pan-Indian representation. This is a meaningful design choice. Many previous Indian genomic studies have been enriched for patients from tertiary urban centres, which underrepresents the country’s rural populations, Northeast communities, coastal groups, and tribal populations — an acknowledged limitation in Indian genomics research more broadly. GAP-India’s multi-centric design is an attempt to address that, though coverage gaps will remain a challenge to monitor as the cohort grows.
Why This Connects to Mental Health and the Whole Person
Parkinson’s disease is not only a movement disorder, and its genetic story is not only a laboratory question. The non-motor burden — anxiety, depression, disrupted sleep, cognitive changes — is where a significant part of the lived experience lives, and it is where the mental health and medical dimensions of the illness meet.
We’ve written before about how chronic physical conditions and depression interact in ways that clinicians often undertreat, and how stigma around seeking help delays care in ways that compound suffering unnecessarily. Those dynamics are especially present in progressive neurological conditions, where patients may be navigating both the physical trajectory of the disease and the emotional weight of a diagnosis that changes how they see their future.
The genetic work matters here too, in a practical sense. If clinicians understand that a patient carries a particular variant — in GBA1, for instance, which is associated with more rapid cognitive decline in some cohorts — that changes the conversation about monitoring, support, and what to prepare for. Genetics doesn’t determine everything. But it gives patients and their families more accurate maps, and more accurate maps allow better decisions.
India’s Parkinson’s genetics research is at an early but genuinely exciting inflection point. The infrastructure now exists, the data is beginning to accumulate, and the findings are already telling a story that the European-anchored literature couldn’t have told. The next several years — as GAP-India matures, as the 2025 GWAS preprint moves through peer review, and as replication cohorts are established — will determine how much of that story we can act on.
References
- Kishore, A. et al. (2025). “Deciphering the Genetic Architecture of Parkinson’s Disease in India.” medRxiv preprint, posted February 21, 2025. DOI: 10.1101/2025.02.17.25322132. (Peer review pending as of June 2026.) — https://www.medrxiv.org/content/10.1101/2025.02.17.25322132v1.full
- Bandres-Ciga, S. et al. (2021). “Genetic Architecture of Parkinson’s Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps.” Frontiers in Neurology / PMC — https://pmc.ncbi.nlm.nih.gov/articles/PMC7323575/
- The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson’s Disease in India. Movement Disorders (2023) / medRxiv preprint (2023). — https://www.medrxiv.org/content/10.1101/2023.06.18.23291407v1
- Nalls, M.A. et al. (2019). “Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies.” Lancet Neurology, 18(12), 1091–1102. https://pubmed.ncbi.nlm.nih.gov/31701892/
- GenomeIndia Project — Mapping genetic diversity with the GenomeIndia project. Nature Genetics, Volume 57, April 2025 — https://genomeindia.in/
- Unlocking India’s Genetic Code: Revelations and Challenges in Parkinson’s Disease Research — https://www.movementdisordersclinic.com/unlocking-indias-genetic-code-revelations-and-challenges-in-parkinsons-disease-research/
Further Reading
On Doctor Mentis:
- Polysomnographic for When the Tremor Doesn’t Let You Sleep: Understanding Sleep Disorders in Essential Tremor
- Chronic Pain and Depression: Breaking Down the Connection
- Breaking the Stigma: Why It’s Okay to Seek Therapy
- Tele MANAS: India’s Mental Health App That’s Bigger Than You Think
External:
- Lux-GIANT Collaboration — www.lux-giant.com
- Parkinson’s Foundation — Understanding PD Genetics
- GenomeIndia Project
Note: This article is for informational purposes only and does not constitute medical advice. For personalised guidance, please consult a qualified neurologist or healthcare professional.
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