Pakistan Genome Resource (PGR), It revealed one of the largest genomic studies ever conducted in South Asia New insights into gene function, disease susceptibility, and translatability of preclinical findings to humans. Published in A nature conditionIt was examined in collaboration between Novartis, Columbia University Irving Medical Center, and the Center for Non-Communicable Diseases in Karachi, Pakistan. 173,303 PGR participants, making up 0.07% of the population of Pakistan, the world’s fifth most populous country.
The numbers alone are impressive, with scientists identifying more than 6.6 million coding genetic variants, with nearly half missing from current global databases. But the PGR is particularly powerful not only because of its size but also because of the unique genetic structure of the populations studied with high levels of familial connection.
The study identified naturally occurring homologous loss-of-function variants in 6,476 genes, about one-third of all human protein-coding genes. The researchers confirmed several known genetic associations. For example, individuals carrying LoF variants in Your father3 The gene had significantly lower triglyceride levels, while variants in PCSK9 It has been linked to lower LDL cholesterol. While both genes are already considered important targets in cardiovascular medicine, the results support the validity of the data set.
New links between genes and biological traits provide clues about conditions ranging from obesity and diabetes to liver disease and neurodegeneration. In one striking example, individuals lack a functional copy of a gene CIDEBwhich has become a major target in metabolism research because rare mutations that inactivate the gene provide significant protection against liver disease, appear to be less susceptible to liver disease, strengthening the case for therapies targeting this pathway.
Some of the findings provided new context for genes that had already been extensively studied, e.g LRRK2– A gene currently targeted by experimental Parkinson’s disease treatments. LoF mutations in LRRK2 Signs of kidney dysfunction appeared. It’s an observation that raises important safety questions and highlights why human genetic studies are important. Sometimes biologics send out a warning before a drug reaches the market.
The research also challenged assumptions based on animal studies. Gene called BRDM9 It is essential for fertility in mice. However, many people in the PGR who had completely inactive versions of the gene had healthy children.
Ultimately, the Pakistani genome resource is much more than just a national database. It’s a reminder that human genetic diversity remains largely unexplored. By studying historically overlooked populations, researchers are uncovering entirely new biology that could lead to better treatments, safer medicines, and a deeper understanding of what makes us human.
