ISLAMABAD: A landmark study involving 173,303 Pakistanis has identified more than 3.1 million previously unknown genetic variants, creating one of world’s largest genomic resources and offering new insights into inherited and lifestyle-related diseases.
The diseases include heart ailment, diabetes, obesity, fatty liver problem, and Parkinson’s disease.
Researchers say these findings could pave the way for safer and more effective treatments.
Led by Prof Danish Saleheen, Dr Asif Rasheed, and Prof Shahzad Ali Khan, the study, published in prestigious journal Nature, addresses a major gap in global medical research and provides a comprehensive genetic reference for Pakistan.
The research is based on Pakistan Genome Resource (PGR), a biobank containing whole-exome and whole-genome sequences from individuals recruited from 23 cities across the country.
The study confirmed several known gene-disease associations while also revealing new insights into cardiovascular disease, diabetes, obesity, liver disease, and neurological disorders.
Some 30.6 percent of participants reported their parents were first cousins, making Pakistani population particularly valuable for identifying disease-causing genes and discovering new drug targets.
Researchers identified genetic variants linked to lower levels of harmful cholesterol and triglycerides, reinforcing existing cholesterol-lowering therapies. They also found some naturally inactive genes appeared to protect against fatty liver disease and could become targets for future medications.
Observations involving genes associated with Parkinson’s disease provided important information for development of safer therapies.
Prof Shahzad Ali Khan, Vice Chancellor of Health Services Academy (HSA), described research as a landmark study and noted the institution collaborated in conducting it. He said findings would help scientists better understand inherited and lifestyle-related diseases affecting Pakistanis and could lead to earlier diagnosis, disease prevention, and the development of more precise and effective treatments tailored to the country’s population.
The research team analysed 166,625 exomes and 6,678 whole genomes, identifying more than 6.6 million genetic changes across 19,021 genes. Of these, over 3.1 million variants had never previously been observed in non-South Asian populations. Nearly two million were entirely new compared to international genetic databases.
Researchers also discovered naturally inactive forms of 6,476 genes, representing nearly one-third of all human protein-coding genes. More than 2,200 of these genes had never before been identified in this inactive state anywhere in the world. One in every five participants carried at least one such inactive gene.
According to Dr Lubna Kamani, one of researchers, the project is particularly significant for Pakistan, where inherited disorders are relatively common due to the high prevalence of marriages among relatives.
Scientists said the genomic resource could eventually help doctors identify individuals at increased risk of disease before symptoms appear, improve the diagnosis of rare inherited conditions, and advance precision medicine, in which treatments are tailored to a person’s unique genetic makeup.
The study was led by Prof Danish Saleheen and Dr Asif Rasheed in collaboration with an international team and Pakistani researchers, including Dr Shareef Khalid, Dr Maleeha Zaman Khan, Dr Lubna Kamani, Prof. Shahzad Ali Khan, Muhammad Jahanzaib, Muhammad Rehan Mian, and several others from institutions across Pakistan.
Whole-exome sequencing data generated as part of the study was funded by Regeneron Pharmaceuticals, AstraZeneca, Novartis, and Astellas Pharma Inc., with additional support from the US National Institutes of Health (NIH).
The research was approved by Institutional Review Board of the Center for Non-Communicable Diseases and National Bioethics Committee of Pakistan, and all participants provided written informed consent.
