BERKELEY, CALIFORNIA – Scientists have completed the largest genetic study of Indian populations, analyzing 2,762 whole-genome sequences that reveal 50,000 years of evolutionary history and identify over 160,000 previously unknown disease-causing genetic variants with implications for billions of people worldwide.
The research team from University of California Berkeley and international collaborators examined genetic data from 18 Indian states and territories as part of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD). The study represents the most comprehensive genetic survey of Indian populations, including diverse geographic regions, language groups, and historically underrepresented communities.
The analysis revealed that modern Indians carry ancestry from three main ancient groups: South Asian hunter-gatherers, Iranian farmers from around 4,000 BCE, and Eurasian steppe pastoralists. Most significantly, (Kerdoncuff et al., 2025) discovered that Indians possess the highest levels of Neanderthal ancestry variation among all modern human populations, with 1-2% of their genetic material inherited from ancient human relatives.
Unprecedented Disease Variant Discovery
The research identified over 160,000 genetic variants associated with diseases that have never been documented in previous genomic studies. These variants affect genes involved in blood disorders, metabolic diseases, drug responses, and complex conditions including cognitive decline and dementia. Many of these disease-causing variants appear only in Indian populations and remain absent from genetic databases based on European or East Asian populations.
“Indians exhibit the largest variation and possess the highest amount of population-specific Neanderthal ancestry segments among worldwide groups,” the researchers reported in their Cell journal publication.
The study found that these unique genetic variants occur at low frequencies across India but can be relatively common within specific communities. For example, researchers identified a pathogenic variant called L307P that causes BCHE deficiency, which appears frequently in certain Indian populations but remains rare globally.
Founder Effects Shape Disease Patterns
The research revealed extensive genetic relatedness among Indians due to historical founder events and cultural practices like endogamy (marriage within specific groups). Each individual in the study of 2,700 people had at least one fourth-degree cousin or closer relative within the sample, demonstrating unprecedented levels of genetic connection.
Indians show homozygosity levels (identical genetic copies from both parents) that are two to nine times higher than Europeans and East Asians. This increased homozygosity raises the prevalence of recessive diseases, where individuals need two copies of a harmful variant to develop the condition.
Ancient Human Inheritance Affects Modern Health
The study found that genetic material inherited from Neanderthals and Denisovans contributes to both adaptation and disease susceptibility in modern Indians. Several archaic variants are concentrated in genes controlling immune system function, including regions that influence responses to infections and autoimmune disorders.
“Leveraging this knowledge could help develop novel therapeutics tailored to Indian populations, particularly for diseases with immune-related components, such as autoimmune disorders and infectious diseases,” the research team explained.
Global Medical Research Implications
The findings have significant implications for personalized medicine and drug development for South Asian populations worldwide. Current medical research predominantly uses genetic data from European populations, potentially missing important disease variants that affect the 1.4 billion people of Indian ancestry globally.
The research provides a comprehensive genetic reference that could improve medical care for Indian populations in India, as well as diaspora communities in countries like the United States, United Kingdom, and Canada. The unique genetic variants identified could explain why certain diseases affect South Asian populations differently and why some medications work differently in these communities.
The study analyzed whole-genome sequences from 2,762 individuals aged 60 and older across 18 Indian states and territories, with approximately equal numbers of males and females representing diverse linguistic, geographic, and social groups throughout the subcontinent.
Key Takeaways
- Scientists discovered over 160,000 new disease variants in Indian populations that could transform medical care for billions globally.
- Indians possess the highest Neanderthal ancestry variation worldwide, with genetic founder effects increasing disease susceptibility in communities.
- Researchers developed comprehensive genetic reference enabling personalized medicine approaches specifically tailored for South Asian populations and diaspora communities.
Related Articles
- Personalized Medicine Based on Genetic Ancestry and Population History – Explore how genetic background influences drug responses and disease risk across different populations.
- Neanderthal DNA in Modern Humans Affects Health and Disease – Learn how ancient human genetic material continues to influence modern health and medical conditions.
- Population Genetics Revolution in Medical Research and Drug Development – Discover how understanding genetic diversity improves medical treatments and reduces health disparities worldwide.
Reference
Kerdoncuff, E., Skov, L., Patterson, N., Banerjee, J., Khobragade, P., Chakrabarti, S. S., Chakrawarty, A., Chatterjee, P., Dhar, M., Gupta, M., John, J. P., Koul, P. A., Lehl, S. S., Mohanty, R. R., Padmaja, M., Perianayagam, A., Rajguru, C., Sankhe, L., Talukdar, A., Varghese, M., Yadati, S. R., Zhao, W., Leung, Y. Y., Schellenberg, G. D., Wang, Y. Z., Smith, J. A., Dey, S., Ganna, A., Dey, A. B., Kardia, S. L. R., Lee, J., & Moorjani, P. (2025). 50,000 years of evolutionary history of India: Impact on health and disease variation. Cell, 188(13), 3389-3404.e6. https://doi.org/10.1016/j.cell.2025.04.027
