Brain Volume Genetic Links to Parkinson’s and ADHD Found

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Researchers have identified 254 genetic variants that influence critical structures in the “deep brain,” such as those that regulate memory, motor skills, and addictive behaviors, in one of the most extensive ever studies of DNA and brain volume.

The study1 is powered by the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, an international effort based at the Keck School of Medicine of USC, which unites more than 1,000 research labs across 45 countries to hunt for genetic variations that affect the brain’s structure and function.

“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’re beginning to home in on what has been called ‘the genetic essence of humanity,'”

said Paul M. Thompson, Ph.D., associate director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute and principal investigator for ENIGMA.

Deep Brain Regions

Identifying brain regions that are either enlarged or diminished in certain groups, such as individuals with a specific neurological disorder, can assist scientists in elucidating the underlying causes of brain dysfunction. Identifying the genes that regulate the development of specific brain regions provides more insight into potential interventions.

In the study, a team of 189 researchers from around the world collected DNA samples and magnetic resonance imaging brain scans, which measured volume in key subcortical regions — also known as the “deep brain” — from 74,898 participants.

The researchers subsequently conducted genome-wide association studies (GWAS), a method that can identify genetic variations associated with a variety of traits or diseases. They discovered several gene-brain volume associations that were associated with a higher risk of Parkinson’s disease and attention-deficit/hyperactivity disorder (ADHD).

“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,”

said principal investigator Miguel Rentería, Ph.D., an associate professor of computational neurogenomics at the Queensland Institute of Medical Research (QIMR Berghofer) in Australia.

Brain Volume Gene Variants

The researchers examined brain volume in critical subcortical areas, such as the brainstem, hippocampus, amygdala, thalamus, nucleus accumbens, putamen, caudate nucleus, globus pallidus, and ventral diencephalon. These regions are essential for memory formation, emotional regulation, motor control, sensory input processing, and responses to reward and punishment.

Genome-wide association studies identified 254 genetic variations linked to brain volume in various locations, accounting for up to 10% of the reported variability in brain volume among study participants. Although prior studies have established connections between certain brain regions and diseases, such as the association of the basal ganglia with Parkinson’s disease, the recent research elucidates the gene variants that more accurately influence brain volume.

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, stated that this paper, for the first time, pinpoints the precise location in the brain where these genes act, thereby establishing the foundation of a roadmap for intervention.

The researchers note that the study is correlational, so more investigation is needed before genes can be causally linked with various diseases.

  1. García-Marín, L.M., Campos, A.I., Diaz-Torres, S. et al. Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries. Nat Genet (2024). Doi: 10.1038/s41588-024-01951-z