Unraveling the Genetic Blueprint of the Deep Brain

Researchers have discovered 254 genetic variations that influence important “deep brain” structures, such as those that govern memory, motor skills, addictive behaviors, and more, in one of the biggest-ever investigations of DNA and brain volume. The journal Nature Genetics published the study.

The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, headquartered at USC's Keck School of Medicine, is driving the study. It brings together over 1,000 research labs in 45 countries to search for genetic variations that impact the structure and function of the brain.

A lot of brain diseases are known to be partially genetic, but from a scientific point of view, we want to find the specific changes in the genetic code that cause these. By conducting this research all over the world, we are beginning to home in on what has been called ‘the genetic essence of humanity.”

Paul M. Thompson, PhD, Associate Director, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California

Thompson is also a Principal Investigator in Enhancing Neuro Imaging Genetics through Meta-Analysis

Scientists can begin to understand what causes brain dysfunction by identifying brain regions that are larger or smaller in some groups (for example, those with a specific brain disease) compared to others. Identifying the genes that govern the development of certain brain regions can provide an additional hint about how to act.

A team of 189 researchers from around the world gathered DNA samples and magnetic resonance imaging brain scans from 74,898 participants in the current study, which was partially supported by the National Institutes of Health.

These scans examined the volume in important subcortical regions, also known as the “deep brain.” Following that, they conducted genome-wide association studies, or GWAS, which are a method for detecting genetic differences associated with different traits or diseases.

They discovered several gene-brain volume connections that carried a higher risk for attention-deficit/hyperactivity disorder (ADHD) and Parkinson's disease.

There is strong evidence that ADHD and Parkinson’s have a biological basis, and this research is a necessary step to understanding and eventually treating these conditions more effectively. Our findings suggest that genetic influences that underpin individual differences in brain structure may be fundamental to understanding the underlying causes of brain-related disorders.”

 Miguel Rentería, PhD, Associate Professor and Study Principal Investigator, Computational Neurogenomics, Queensland Institute of Medical Research

Studying the Deep Brain

The researchers measured the volume of the brain in the brainstem, hippocampus, amygdala, thalamus, nucleus accumbens, putamen, caudate nucleus, globus pallidus, and ventral diencephalon, among other important subcortical regions.

These areas are essential for memory formation, emotion regulation, motor control, processing sensory information from the environment, and reacting to rewards and penalties.

GWAS identified 254 genetic variations linked to brain volume in those areas, which could account for as much as 10% of the reported variations in brain volume across study participants.

The new study identifies which gene mutations shape brain volume more precisely, even if prior research has associated specific regions with disease, such as the basal ganglia with Parkinson's disease.

“This paper, for the first time, pinpoints exactly where these genes act in the brain,” providing the beginnings of a roadmap for where to intervene said Thompson, who is also a Professor of Ophthalmology, Pediatrics, Neurology, Psychiatry, and the Behavioral Sciences, Radiology, Biomedical Engineering and Electrical Engineering at the Keck School of Medicine.

The study is correlational, so further research is required before genes may be causally connected to different diseases, the researchers said.