The findings of this study are a landmark in the field of neurogenetics, expanding our understanding of how genetic variation influences the development and functioning of the deep brain. They also reinforce the connection between these variations and neuropsychiatric diseases such as ADHD and Parkinson’s. However, more research is needed to confirm causal relationships and explore how these insights can be translated into more effective treatments for brain disorders.
The brain’s subcortical structures play key roles in developmental disorders, psychiatric conditions, and neurological diseases.
These areas include deep brain regions responsible for functions such as memory, motor control, emotional regulation, and the processing of rewards and punishments.
A new study, led by researchers at the University of Queensland and published in the journal Nature Genetics, has made significant advances in our understanding of these structures by identifying genetic variations associated with their volume.
Locations of subcortical regions. Each region is labeled with a different color. Source: Zhenni Gao et al. August 2021. Brain Structure and Function 226(10):1-11. DOI: 10.1007/s00429-021-02355-z
In the largest study of its kind to date, scientists analyzed DNA samples and MRI scans from 74,898 individuals of European ancestry.
They performed genome-wide association studies (GWAS) to examine intracranial volume and that of nine subcortical regions: the brainstem, hippocampus, amygdala, thalamus, nucleus accumbens, putamen, caudate nucleus, globus pallidus, and ventral diencephalon.
Using this approach, the researchers identified 254 independent genetic loci that influence the volume of these regions, explaining up to 35% of the variation observed between participants.
Genetic loci refer to specific positions occupied by a gene or a DNA sequence in the genome, usually on a chromosome. In the context of studies such as GWAS, as in the text we discussed, “independent loci” refer to regions of the genome where specific genetic variants have been identified as being associated with a trait or condition. Each independent locus points to a genetic region that contributes to a characteristic without redundancy with other identified loci.
These genetic loci have also been associated with gene expression in specific types of neural cells, at different times in their differentiation.
Genes related to intracellular signaling and brain aging processes have been highlighted, suggesting a relationship with brain development and degeneration.
Genome-wide association study (GWAS) is nothing more than a tool used to study the relationship between phenotypic characteristics and genotype. Source: Wasana Sukhumsirichart. Genetic Diversity and Disease Susceptibility. DOI: 10.5772/intechopen.76728
In addition to mapping the genetic variations that shape brain volume, the study explored the connection of these variants with diseases such as attention-deficit/hyperactivity disorder (ADHD) and Parkinson's disease.
The analysis revealed evidence that changes in the volumes of subcortical structures are linked to an increased genetic risk for these conditions.
According to the researchers, these findings are a crucial step toward understanding the biological basis of brain disorders.
They also highlight that the genetic influences responsible for individual differences in brain structure may be key to understanding the underlying causes of brain-related diseases.
The study was conducted in partnership with the international consortium ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis), an initiative that brings together more than a thousand research laboratories from 45 countries. ENIGMA's mission is to investigate genetic variations that affect brain structure and function, joining forces to uncover the biological mechanisms underlying neurological and psychiatric conditions.
One of the goals of this research is to identify brain regions that exhibit structural differences between groups, such as people with certain diseases, and to investigate how specific genes control the development of these areas.
These findings could provide important clues for therapeutic interventions by directly pinpointing where genes act in the brain.
Although this study is correlational, representing associations between genes and brain structures, it lays a valuable foundation for future research. This is the first study to precisely locate where genes act in the brain. This initial knowledge could serve as a roadmap for interventions aimed at correcting brain dysfunctions in different conditions.
The findings of this study are a milestone in the field of neurogenetics, expanding our understanding of how genetic variation influences the development and functioning of the deep brain.
They also reinforce the connection between these variations and neuropsychiatric diseases, such as ADHD and Parkinson’s. However, more research is needed to confirm causal relationships and explore how these insights can be translated into more effective treatments for brain disorders.
READ MORE:
Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.
García-Marín LM, Campos AI, Diaz-Torres S. et al.
Nat Genet 56, 2333–2344 (2024).
Abstract:
Subcortical brain structures are involved in developmental, psychiatric, and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala, and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.
Comentarios