Pakistani genomes reveal 34,000 knockouts that could explain why mouse-based drugs fail in humans

A comprehensive analysis of 173,303 genomes from Pakistan, published today in Nature, is upending how scientists understand human genetics and drug development. By identifying 34,000 people who are "human knockouts," with complete loss of function of at least one gene, the study reveals variation in the human genome needed to shape new treatments for human diseases while also illuminating why drugs developed in mice often fail in humans.
Analysis of 173,303 Pakistani genomes identified ~34,000 individuals with complete loss-of-function in ≥1 gene, yielding knockouts in ~6,500 protein-coding genes. Many genes deemed essential from mouse models are variable in humans, clarifying failures of mouse-based drug targets (e.g., RXFP1) and highlighting protective knockouts (e.g., CIDEB) as therapeutic candidates. The resource improves prediction of drug efficacy and safety, including ancestry-translatable insights, and demonstrates the value of consanguineous South Asian populations for human genetics and drug development.
Crucially, the study reveals that genes considered "essential" to life and intolerant to changes, based on mouse models, are actually variable in humans—a finding with profound implications for pharmaceutical development.

The genomes also contain information needed to uncover the functions of two-thirds of human genes that remain a mystery even 25 years after the completion of the Human Genome Project.

Allan Gurtan, Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource, Nature (2026). DOI: 10.1038/s41586-026-10667-5. www.nature.com/articles/s41586-026-10667-5

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How early life experiences shape schizophrenia risk

Researchers have found that childhood trauma, poverty, social isolation and other adverse life experiences are associated with brain changes linked to schizophrenia-spectrum disorders—findings that could help researchers identify people at risk earlier and develop interventions before severe symptoms emerge.
Early-life adversity, including trauma, poverty, social isolation, discrimination, and food insecurity, is associated with alterations in brain structure, function, and neurochemistry linked to schizophrenia-spectrum disorders. These factors do not singly cause schizophrenia but increase risk in vulnerable individuals. Understanding these neurobiological pathways may enable earlier, more targeted, and potentially preventive interventions.
Overall, the researchers found evidence that greater exposure to adverse conditions early in life is associated with differences in brain structure, brain function and neurochemistry—all of which have been previously linked to schizophrenia-spectrum disorders.

Social Determinants of Health and Neurobiology Across the Schizophrenia Course: A Systematic Review, JAMA Psychiatry (2026). DOI: 10.1001/jamapsychiatry.2026.1312

The kombucha paradox: Measurable effects, uncertain well-being benefits

Kombucha has become part of the wider boom in gut-friendly foods and drinks. But a major heart health charity is urging consumers to look more carefully at what these products actually contain.
The British Heart Foundation has warned that some popular gut-friendly products can come with drawbacks. Commercial kombucha may be a healthier alternative to some sugary fizzy drinks, but store-bought versions can contain added sugar. Other fermented foods, such as kimchi and sauerkraut, can be high in salt.

The warning points to a wider problem. Foods and drinks sold with a health halo are not always straightforwardly healthy. The fact that a product contains potentially active compounds does not prove it will produce a meaningful benefit.

Kombucha is often sold as more than a fizzy drink. Because it is fermented, it is commonly linked with gut health, well-being and even stress resilience.

But in a controlled human study, the results were more complicated. Drinking kombucha each day changed some metabolic markers in the body, but did not clearly change how healthy adults responded to acute laboratory stress.
But it tells us something important: Biological activity does not automatically mean a meaningful health benefit.
Daily consumption of a controlled kombucha drink for eight weeks altered metabolic biomarkers but did not meaningfully change acute stress responses, including cortisol, autonomic measures, or self-reported stress, compared with placebo in healthy adults. Kombucha’s measurable biological activity therefore does not translate into demonstrated well-being or stress-resilience benefits, and health claims remain unsupported.

original article.