A consortium of researchers has created the largest and most advanced multidimensional maps of gene regulatory networks in the brains of people with and without mental disorders. These maps detail the many regulatory elements that coordinate the brain’s biological pathways and cellular functions. The research, supported by the National Institutes of Health (NIH), used postmortem brain tissue from more than 2,500 donors to map gene regulatory networks in various stages of brain development and multiple brain-related disorders.
These ground-breaking findings advance our understanding of where, how, and when genetic risk contributes to mental disorders such as schizophrenia, post-traumatic stress disorder and depression. Furthermore, the critical resources, which are freely shared, I will help researchers identify genetic variants likely to play a causal role in mental illness and identify potential molecular targets for new therapeutics.”
Joshua A. Gordon, MD, Ph.D., Director of NIH’s National Institute of Mental Health (NIMH)
The research is published in 15 papers in Science, Advances in Scienceand Scientific Reports. The papers report findings on several key themes:
- Population-level analyzes linking genetic variants, regulatory elements, and different molecular patterns of gene expression to cellular-level regulatory networks in both the developing and adult brains
- Single-cell-level maps of prefrontal cortex from individuals diagnosed with mental disorders and neurodevelopmental disorders
- Experimental analyzes validating the function of regulatory elements and genetic variants associated with quantitative trait loci (segments of DNA associated with observable traits)
The analyzes expand on previous findings by investigating multiple cortical and subcortical regions of the human brain. These brain regions play key roles in a number of basic processes, including decision-making, memory, learning, emotion, reward processing and motor control.
About 2% of the human genome consists of protein-coding genes. The remaining 98% includes segments of DNA that help regulate the activity of these genes. To better understand how brain structure and function contribute to mental disorders, researchers in the NIMH-funded PsychENCODE consortium are using standardized methods and data analysis approaches to build a comprehensive picture of these regulatory elements in the human brain.
In addition to these discoveries, the papers also highlight new methods and tools to help researchers analyze and explore the wealth of data generated by this effort. These resources include an online platform that offers interactive imaging data from various types of brain cells in people with and without mental disorders, known as PsychSCREEN. Together, these methods and tools provide a comprehensive, comprehensive data source for the wider research community.
The work focuses on the second phase of findings from the PsychENCODE Consortium. This effort aims to advance our understanding of how gene regulation affects brain function and dysfunction.
“These PsychENCODE Consortium findings shed new light on how genetic risk maps to brain function across developmental stages, brain regions and disorders,” said Jonathan Pevsner, Ph.D., chief of the NIMH Genomics Research Branch. “The work lays a strong foundation for continued efforts to characterize regulatory pathways in disorders, elucidate the role of epigenetic mechanisms, and increase the ancestral diversity represented in studies.”
PsychENCODE papers published in Science and Advances in Science presented as a collection at Science Website.
