NIH-funded research details cellular and molecular regulatory elements of the brain and their impact on brain function
• Press release
A consortium of researchers has produced 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 numerous regulatory elements that coordinate biological pathways and cellular functions in the brain. 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 at different stages of brain development and multiple brain-related disorders.
“These groundbreaking findings improve our understanding of where, how, and when genetic risk contributes to mental disorders such as schizophrenia, post-traumatic stress disorder, and depression,” said Joshua A. Gordon, M.D., Ph.D., director of the NIH. . National Institute of Mental Health (NIMH). “In addition, critical resources, freely shared, will help researchers identify genetic variants that likely play a causal role in mental illness and identify potential molecular targets for new therapies.”
The research is published in 15 articles in Science, Scientific advancesand Scientific Reports . The articles report findings on several key topics:
- Population-level analyzes linking genetic variants, regulatory elements and different molecular forms of expressed genes with regulatory networks at the cellular level, both in the developing brain and the adult brain.
- Single-cell maps of the prefrontal cortex of individuals diagnosed with mental disorders and neurodevelopmental disorders
- Experimental analyzes validating the role of regulatory elements and genetic variants associated with quantitative trait loci (DNA segments that are linked to observable traits)
The analyzes extend previous findings and explore multiple cortical and subcortical regions of the human brain. These brain areas play key roles in a variety of essential processes, including decision-making, memory, learning, emotions, reward processing, and motor control.
Approximately 2% of the human genome is made up of protein-coding genes. The remaining 98% includes segments of DNA that help regulate the activity of those genes. To better understand how brain structure and function contribute to mental disorders, researchers from the NIMH-funded PsychENCODE Consortium are using standardized methods and data analysis approaches to build a complete picture of these regulatory elements in the human brain.
In addition to these discoveries, the articles also highlight new methods and tools to help researchers analyze and explore the wealth of data produced by this effort. These resources include a web-based platform that offers interactive visualization of data from various types of brain cells in people with and without mental disorders, known as Psychoscreen . Together, these methods and tools provide a comprehensive and integrated data resource for the broader research community.
The articles focus on the second phase of the PsychENCODE Consortium findings. This effort aims to advance our understanding of how gene regulation affects brain function and dysfunction.
“These findings from the PsychENCODE Consortium shed new light on how genetic risk maps to brain function across all stages of development, brain regions, and disorders,” said Jonathan Pevsner, Ph.D., head of the Genomic Research Branch of the NIMH. “The work lays a solid foundation for ongoing efforts to characterize the regulatory pathways of disorders, elucidate the role of epigenetic mechanisms, and increase the ancestral diversity represented in studies.”
PsychENCODE articles are presented as a collection in the Science website .
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About the National Institute of Mental Health (NIMH): The mission of
NIMH
is to transform the understanding and treatment of mental illness through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and medical research. translational, and is investigating the causes, treatments and cures of common and rare diseases. For more information about NIH and its programs, visit the NIH website .
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