Researchers have developed a genomic mapping technique that reveals how thousands of genes work together to influence disease risk, helping to bridge gaps left by traditional genetic studies. The approach, described in a Nature paper led by Gladstone Institutes and Stanford University scientists, combines large-scale cell experiments with population genetics data to highlight promising targets for future therapies and deepen understanding of conditions such as blood disorders and immune-mediated diseases.
Biomedical scientists have long sought to identify genes that contribute to illness, but many common diseases involve intricate networks of multiple genes, making it difficult to translate genetic signals into effective treatments. A study published in the December 10, 2025, issue of Nature, titled "Causal modelling of gene effects from regulators to programs to traits," introduces a genomic mapping strategy designed to close that gap.
According to materials from Gladstone Institutes, the method was developed by researchers at Gladstone and Stanford University and uses a broad screening approach that tests the impact of essentially every gene in a cell, linking diseases and other traits to the underlying genetic systems that shape them.
"We can now look across every gene in the genome and get a sense of how each one affects a particular cell type," said Alex Marson, MD, PhD, a senior investigator at Gladstone and co-leader of the study, in a statement released by Gladstone Institutes. The team, led by first author Mineto Ota, MD, PhD, combined functional data from human blood cell experiments with genomic information from large population resources to uncover how gene perturbations ripple through cellular programs.
As described in the ScienceDaily summary of the work, the researchers mapped how switching off or altering genes in blood cells affected traits related to red blood cell biology, and then integrated these results with large-scale genetic association data to trace the pathways from specific regulators to cellular programs to clinical traits.
One prominent example highlighted in the study is the gene SUPT5H, which is associated with beta thalassemia, a blood disorder that disrupts hemoglobin production and can lead to moderate to severe anemia. The team connected SUPT5H to three key blood cell processes: hemoglobin production, the cell cycle, and autophagy, and showed that the gene can increase or decrease activity in each of these programs.
"SUPT5H regulates all three main pathways that affect hemoglobin," said co-leader Jonathan Pritchard, PhD, a professor of biology and genetics at Stanford, in comments reported by Gladstone Institutes. "It activates hemoglobin synthesis, slows down the cell cycle, and slows down autophagy, which together have a synergistic effect."
Although the first maps focus on blood cells, the researchers emphasize that the technique can be applied to many other human cell types. For immunology in particular, Marson's lab, which studies T cells and other immune cells, expects to use the approach to probe autoimmune diseases, immune deficiencies, and allergies, areas where genetic risk is strongly enriched in T cells.
"The genetic burden associated with many autoimmune diseases, immune deficiencies, and allergies are overwhelmingly linked to T cells," Marson said in the Gladstone release. "We look forward to developing additional detailed maps that will help us really understand the genetic architecture behind these immune-mediated diseases."
The study was funded by a number of organizations, including the National Institutes of Health and the Simons Foundation, as well as other philanthropic and institutional supporters listed by Gladstone Institutes. The researchers say the resulting gene–network maps could help accelerate drug development by pinpointing the most influential genes and pathways in complex diseases.
