In one of the largest studies of DNA and brain volume in history, researchers have identified 254 genetic variants that shape key “deep brain” structures, including those that control memory, motor skills, addictive behaviors and more. The results have just been published in a journal. Natural genetics.

The research is being conducted by the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) consortium, an international initiative based at the Keck School of Medicine of the University of Southern California that brings together more than 1,000 research laboratories in 45 countries to search for genetic variations that influence brain structure and function.

“Many brain diseases are known to be partly genetic, but scientifically we want to find the specific changes in the genetic code that cause them,” said Paul M. Thompson, Ph.D., associate director of the University of Southern California. Mark and Mary Stevens Institute for Neuroimaging and Computer Science and ENIGMA Principal Investigator.

“By doing these studies around the world, we are starting to get closer to what is called the ‘genetic essence of humanity,'” he said.

Identifying areas of the brain that are larger or smaller in some groups (such as people with a certain brain disease) compared to others can help scientists begin to understand what causes brain dysfunction. Finding genes that control the development of these brain regions provides additional clues about how to intervene.

In the present study, funded in part by the National Institutes of Health, a team of 189 researchers from around the world collected DNA samples and performed magnetic resonance imaging scans of the brain that measured volume in key subcortical regions, also known as the “deep brain.” — from 74,898 participants. They then conducted genome-wide association studies, or GWAS, an approach that can identify genetic variations associated with different traits or diseases, finding some gene and brain volume associations that carry a higher risk of Parkinson’s disease and attention-deficit/hyperactivity disorder (ADHD). ).

“There is compelling evidence that ADHD and Parkinson’s disease have a biological basis, and this study is a necessary step toward understanding and ultimately more effectively treating these conditions,” said Miguel Renteria, Ph.D., assistant professor of computational neurogenomics at Queensland Medical Institute. Researcher (QIMR Berghofer) in Australia and Principal Investigator of the Nature Genetics study.

“Our results suggest that genetic influences underlying individual differences in brain structure may be fundamental to understanding the underlying causes of brain-related diseases,” he said.

Exploring the depths of the brain

The researchers analyzed brain volume in key subcortical structures, including the brainstem, hippocampus, amygdala, thalamus, nucleus accumbens, putamen, caudate nucleus, globus pallidus, and ventral diencephalon. These areas are critical for forming memories, regulating emotions, controlling movement, processing sensory input from the outside world, and responding to reward and punishment.

GWAS identified 254 genetic variants associated with brain volume in these regions, explaining up to 10% of the observed differences in brain volume among study participants. While previous studies have clearly linked certain regions to disease, such as the basal ganglia with Parkinson’s disease, the new study reveals which gene variants shape brain volume with greater precision.

“This paper pinpoints for the first time exactly where these genes operate in the brain,” providing a roadmap for where to intervene, said Thompson, who is also a professor of ophthalmology, pediatrics, neurology, psychiatry and behavioral sciences. , radiology, biomedical engineering and electrical engineering at the Keck School of Medicine.

The researchers note that the study is correlational in nature, so more research is needed before the genes can be causally linked to various diseases.

First authors of the study from Renteria’s group were doctoral student Luis Garcia-Marin and postdoctoral fellow Adrian Campos. In addition to the ENIGMA data, the researchers also used data from the Heart and Aging in Genomic Epidemiology (CHARGE) cohort, the UK Biobank and the Adolescent Brain Cognitive Development (ABCD) study. Summary statistics are available for downloading by researchers on the ENIGMA consortium website.

About this study

In addition to Thompson and Renteria, other USC study authors include Neda Jahanshad and Sophia I. Thomopoulos of the USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC. A complete list of authors and their affiliations can be found in the online publication.

This work was supported by federal and private agencies worldwide, including the National Institutes of Health under grants R01AG058854, U01AG068057, R01NS107513, and R01MH116147. A complete list of sponsors can be found in the online publication.

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