A group of scientists has created extensive maps of gene regulation networks in the brains of individuals with and without mental disorders, using postmortem brain tissue from over 2,500 donors. These detailed maps show the various regulatory elements that control the biological pathways and cellular functions in the brain. The research covers different stages of brain development and various brain-related disorders, providing important insights into brain function.The research, funded by the National Institutes of Health (NIH), used postmortem brain tissue from over 2,500 donors to create maps of gene regulation networks in different stages of brain development and various brain-related disorders. These maps reveal the complex regulatory elements that control the biological pathways and cellular functions of the brain. “These groundbreaking findings enhance our knowledge of the location, manner, and timing of genetic risk in conditions like schizophrenia, post-traumatic stress disorder, and depression,” stated Joshua A. Go.rdon, M.D., Ph.D., director of NIH’s National Institute of Mental Health (NIMH), mentioned that offering critical resources for free will assist researchers in identifying genetic variants that may be the cause of mental illnesses and finding potential molecular targets for new treatments. The research has been published in 15 papers in Science, Science Advances, and Scientific Reports. These papers cover various key themes, including population-level analyses linking genetic variants, regulatory elements, and different molecular forms of expressed genes to regulatory networks.The research focuses on the cellular level of the brain, both in the developing and adult brain. It includes maps of the prefrontal cortex at the single-cell level from individuals with mental and neurodevelopmental disorders. The study also includes experimental analyses to validate the function of regulatory elements and genetic variants associated with observable traits. The analyses build on previous findings and explore various regions of the human brain, which are crucial for processes such as decision-making, memory, and learning., emotion, reward processing, and motor control.
A small fraction, approximately 2%, of the human genome contains genes that are responsible for producing proteins. The remaining 98% consists of DNA segments that play a role in regulating the activity of these genes. Researchers in the NIMH-funded PsychENCODE Consortium are working to gain a better understanding of how brain structure and function contribute to mental disorders. They are using standardized methods and data analysis approaches to create a comprehensive understanding of these regulatory elements in the human brain.
Furthermore, the papers also showcase new methods and tools that can assist researchers in analyzing and exploring the vast amount of data available.The data generated by this project includes a web-based platform called PsychSCREEN, which provides interactive visualizations of data from various types of brain cells in people with and without mental disorders. These resources, along with the methods and tools used, create a comprehensive data source for the wider research community.
The papers concentrate on the second phase of results from the PsychENCODE Consortium, which is working to enhance our knowledge of how gene regulation affects brain function and dysfunction.
“These findings from the PsychENCODE Consortium provide new insights into how genetic risk relates to brain function throughout development.”The research on PsychENCODE papers focuses on understanding the developmental stages, brain regions, and disorders,” explained Jonathan Pevsner, Ph.D., who serves as the chief of the NIMH Genomics Research Branch. ”This work provides a strong foundation for ongoing efforts to identify regulatory pathways across disorders, clarify the role of epigenetic mechanisms, and enhance the ancestral diversity represented in studies.”
