A consortium of researchers has completed the largest and most advanced multidimensional maps of gene regulation networks in the brains of individuals with and without mental disorders. The research, funded by the National Institutes of Health (NIH), utilized postmortem brain tissue from more than 2,500 donors to map gene regulation networks across various stages of brain development and multiple brain-related disorders. These maps provide insight into the regulatory elements that coordinate the brain’s biological pathways and cellular functions, helping to uncover where and how genetic risk contributes to disorders such as schizophrenia, post-traumatic stress disorder, and depression.
The groundbreaking findings have advanced the understanding of genetic risk factors in mental disorders, providing critical resources that are freely shared to assist researchers in identifying genetic variants that may play a causal role in mental illnesses and potential molecular targets for new therapeutics. The research, published across 15 papers in Science, Science Advances, and Scientific Reports, reports on population-level analyses, single-cell-level maps of the prefrontal cortex in individuals with mental disorders, and experimental analyses validating the function of regulatory elements and genetic variants associated with observable traits.
Researchers in the NIMH-funded PsychENCODE Consortium are using standardized methods and data analysis approaches to build a comprehensive understanding of the regulatory elements in the human brain. Approximately 2% of the human genome codes for proteins, while the remaining 98% includes DNA segments that regulate the activity of these genes. The discoveries from this effort offer new insights into how brain structure and function contribute to mental disorders, with new methods and tools developed to help researchers analyze and explore the vast amount of data produced. These resources include a web-based platform called PsychSCREEN, offering interactive visualization data from various brain cell types in individuals with and without mental disorders.
The second phase of findings from the PsychENCODE Consortium focuses on advancing understanding of how gene regulation impacts brain function and dysfunction. These findings shed new light on how gene risk maps onto brain function across different developmental stages, brain regions, and disorders. The work lays a strong foundation for ongoing efforts to characterize regulatory pathways across disorders, elucidate the role of epigenetic mechanisms, and increase ancestral diversity in studies. The papers published in Science and Science Advances are presented as a collection on the Science website, providing a comprehensive and integrated data resource for the broader research community.
Overall, the research from the PsychENCODE Consortium offers valuable insights into the gene regulation networks in the human brain and their role in mental disorders. By mapping these networks across different stages of development and multiple brain regions, researchers have gained a deeper understanding of how genetic risk factors contribute to various mental illnesses. The findings also provide new methods and tools to help researchers analyze and explore the data generated, contributing to ongoing efforts to characterize regulatory pathways, understand epigenetic mechanisms, and enhance diversity in studies. The resources developed as part of this effort will continue to support further research in this important area of study.