Islamabad: A landmark study involving 173,303 Pakistanis has identified more than 3.1 million previously unknown genetic variants, creating one of the world’s largest genomic resources and providing new insights into inherited and lifestyle diseases, including heart disease, diabetes, obesity, fatty liver disease and Parkinson’s disease, which researchers say could lead to safer and more effective treatments.
Lead by Prof Danish Saleheen and Dr Asif Rasheed as well as Prof. Shahzad Ali Khan, authors said the findings, published in the prestigious journal Nature, fill a major gap in global medical research and provide a comprehensive genetic reference for Pakistan. The study is based on the Pakistan Genome Resource (PGR), a biobank comprising whole exome and genome sequences from people recruited from 23 cities across the country.
The study confirmed several known links between genes and diseases and provided fresh insights into cardiovascular disease, diabetes, obesity, liver disease and neurological disorders.
Around 30.6 percent of participants reported that their parents were first cousins, making the Pakistani population especially valuable for identifying disease-causing genes and discovering new drug targets.
Researchers identified genetic variants associated with lower levels of harmful cholesterol and triglycerides, supporting existing cholesterol-lowering therapies, while some naturally inactive genes appeared to protect against fatty liver disease and may serve as targets for future medicines. Observations involving genes linked to Parkinson’s disease also provided important information for developing safer therapies.
Prof Shahzad Ali Khan, Vice Chancellor of the Health Services Academy (HSA), termed it a landmark study and said the institution had collaborated in conducting the research. He said the findings would help scientists better understand inherited and lifestyle diseases affecting Pakistanis and could pave the way for earlier diagnosis, disease prevention and development of more precise and effective treatments tailored to the country’s population.
The team analysed 166,625 exomes and 6,678 whole genomes and identified more than 6.6 million genetic changes in 19,021 genes. Of these, more than 3.1 million variants had not been seen previously in non-South Asian populations, while nearly two million were entirely new compared with international genetic databases.
Researchers 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 state anywhere in the world, while one in every five participants carried at least one such inactive gene.
According to Dr. Lubna Kamani who was one of the researchers, the project has particular significance 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 people at increased risk of diseases before symptoms appear, improve the diagnosis of rare inherited conditions and support precision medicine, in which treatments are tailored to an individual’s 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, Lubna Kamani, Prof Shahzad Ali Khan, Muhammad Jahanzaib, Muhammad Rehan Mian and several others from institutions across the country.
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. The research was approved by the institutional review board of the Center for Non-Communicable Diseases and the National Bioethics Committee of Pakistan, while all participants provided written informed consent.
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