by Beneath the bulging cerebral cortex of the human brain, smaller structures toil in relative obscurity. Subcortical areas, also called the ‘deep brain’, play a key role in functions such as attention, emotion, motor control and learning.
They are also involved in many neurological disorders. Research has linked variations in the volume of subcortical structures to a range of disorders, including schizophrenia, Parkinson’s disease and ADHD.
In a new large-scale study, researchers are shedding light on how 254 genetic variants can influence the development of certain subcortical structures, and potentially influence some important deep-brain operations.
This could help clarify the genetic origins of brain disorders, explains co-author and neuroscientist Paul M. Thompson of the University of Southern California (USC).
“It is known that many brain diseases are partly genetic, but from a scientific point of view we want to find the specific changes in the genetic code that cause them,” says Thompson.
The research represents a massive scientific effort, in which an international team of 189 researchers analyzed genetic data from 74,898 individual participants in 19 countries, as well as MRI brain scans that measure the volume of subcortical regions such as the amygdala, brainstem, hippocampus, putamen, and thalamus.
This was made possible in part by the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, an international project based at USC’s Keck School of Medicine that includes work from more than 1,000 research laboratories in 45 countries.
“By conducting this research around the world, we are beginning to understand what has been called ‘the genetic essence of humanity,'” said Thompson, ENIGMA’s principal investigator.
The team used a research technique known as a genome-wide association study (GWAS), which analyzes variations in DNA sequences in the genomes of large numbers of people to discover markers of different traits or diseases. The study revealed 254 genetic variants associated with volume in several subcortical regions, the authors report, accounting for as much as 10 percent of the observed volume differences between study participants.
It was “the largest GWAS meta-analysis of intracranial and subcortical brain volumes to date,” the researchers write, providing insights into the genetic underpinnings of brain volume variations and associated disorders.
Notably, the study found genetic correlations for eight subcortical brain volumes with Parkinson’s disease and three with ADHD.
Such information is essential for developing better treatments, says Miguel Rentería, associate professor of computational neurogenomics at the Queensland Institute of Medical Research.
“There is strong evidence that ADHD and Parkinson’s have a biological basis, and this research is a necessary step to better understand and ultimately treat these conditions more effectively,” said Rentería, the lead researcher on the new study.
“Our findings suggest that genetic influences underlying individual differences in brain structure may be fundamental to understanding the underlying causes of brain-related disorders.”
Previous studies have already drawn links between certain disorders and subcortical structures, the researchers note, such as Parkinson’s disease and the basal ganglia.
But these findings peel back another major layer, they add, and show us how genetic variants influence the development of crucial brain structures – which in turn could give rise to associated disorders.
The latter remains speculative, the researchers emphasize. But while more research is still needed to prove whether and how exactly genetic variation may be responsible for brain disorders, the new study provides compelling evidence.
“This paper is the first to pinpoint exactly where these genes work in the brain,” says Thompson.
The research was published in Nature genetics.
