The GenomeIndia project has created one of the most comprehensive catalogues of human genetic variation in Indian populations to date. With over 10,000 whole genomes sequenced from 83 population groups in India, the project marks a pivotal step toward understanding India’s vast genetic landscape – an area historically underrepresented in global genomics.
Previously, GenomeAsia, IndiGen and the Longitudinal Aging study of India attempted to fill the gap. Now, GenomeIndia has stepped in with Indo-centric data. GenomeIndia is a collaborative effort of 20 institutions with the Centre for Brain Research at IISc, Bengaluru coordinating the initiative.
To ensure a representative and diverse sample set, the research team collected blood samples from over 20,459 healthy individuals, across 30 tribal and 53 non-tribal populations. The researchers avoided genetic relatedness closer than first cousins within each group. This sampling strategy maximised the detection of population-specific variants, especially in isolated, endogamous populations, which are more likely to harbour rare or unique genetic variants due to their genetic bottlenecks and limited gene flow.
The researchers first genotyped more than 13,000 individuals using a genome-wide single nucleotide polymorphism array. They selected a subset of more than 10,000 individuals for whole genome sequencing. The whole genome sequencing was done at four national centers, ensuring uniform quality control and technical reproducibility. The researchers benchmarked sequencing depth and data quality using known high-confidence samples from the Genome in a Bottle reference set. This helped achieve high recall and precision for single nucleotide variants as well as for insertions and deletions.
Following joint genotyping and rigorous filtering, the research team retained more than 9,000 samples consisting of a more or less equal number of male and female participants. The data yielded approximately 130 million autosomal variants, a substantial number of which were previously undocumented. Over 65 per cent of these variants were ultra-rare with a minor allele frequency of less than one in thousand. This demonstrates the power of the project to reveal population-specific genetic variation.
The researchers developed a reference haplotype panel for genotype imputation in genome-wide association studies. Early tests using this panel showed superior performance over global references when applied to South Asian genomes, underscoring its relevance for research in Indian and diaspora populations.
The immediate benefit for India is the creation of a population-specific genomic resource that can inform precision healthcare and policy-making. The discovery of rare and common pharmacogenetic variants can have direct applications in improving drug safety and efficacy. This has historically been based on European genetic datasets and was, therefore, poorly suited to Indian populations.
The data also serves as a foundation for building more accurate polygenic risk scores for common diseases such as diabetes, cardiovascular disease, and mental illness – conditions with variations among Indian subgroups due to environmental and sociocultural diversity. The data can be accessed at https://genomeindia.in/
The project supports the development of India-specific genotyping arrays, such as an updated version of the South Asian Research Genotyping Array, to enable the identification of low-frequency and ancestry-specific variants for both research and clinical needs. Thus, GenomeIndia contributes to decolonising global genomics, from Europe-derived datasets. In the era of global genomics, GenomeIndia is not just a data-generation effort. It is a step toward equitable precision medicine and public health innovation.
The success of the project has led to plans for increasing coverage in the coming years.
Nature Genetics published online on 8th April 2025;
DOI: 10.1038/s41588-025-02153-x
Reported by Ragothaman M. Yennamalli
SASTRA (Deemed) University, Chennai
STEAMindiaReports 
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