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Genome Snippets Influence Brain Architecture

Study on genetic architecture of cerebral cortex

Jülich/Los Angeles/Herston, 20 March 2020 – Scientists recently investigated the influence of genes on the development of the human brain architecture. The researchers succeeded in identifying more than 300 sites in the human genome that have a major impact on the formation of the brain architecture. More than 360 scientists from 184 research centres were involved in this international study, for which they analysed data from more than 50,000 people. They verified that there are relationships between the architecture of the cerebral cortex and brain function – including dysfunctions such as Parkinson’s, ADHD, depression, and insomnia. The results have been published in the renowned specialist journal Science.

The cerebral cortex is the outer layer of neural tissue in our brains. It is 2–5 mm thick and responsible for smell, hearing and speech, tactile sense and taste, vision, movement, and thinking. The cerebral cortex is the basis of our complex cognitive abilities.

It is already known that the differences in the architecture of the cerebral cortex between individuals, particularly in terms of surface area and thickness, have an influence on our neurological and psychological characteristics, such as our behaviour. However, the question of what genetic factors influence this variability of the cerebral cortex has not previously been systematically investigated.

The international ENIGMA research consortium (Enhancing Neuro Imaging Genetics through Meta-Analysis) has therefore conducted a large-scale study on how genetic variants influence the architecture of the cerebral cortex. The scientists analysed brain scans of 51,665 adults, from which data on the surface area and thickness in 34 sites (“loci”) were determined. The researchers then matched these data, which were obtained from 60 population-based cohort studies, including Forschungszentrum Jülich’s 1000BRAINS study, to up to 10 million variable loci in the genome.

For their analysis, the researchers used genome snippets called SNPs (pronounced “snips”). “These are markers for frequently occurring differences in individual DNA building blocks, which make up the largest part of genetic variability in humans,” explains Sven Cichon, human geneticist and working group leader at Jülich’s Institute of Neuroscience and Medicine. “A typical SNP is a locus in the genome at which two varieties occur in the overall population, for example either cytosine or thymine as DNA building blocks.” SNPs are evenly distributed over the DNA of a person, with several million of them in the genome of one person alone. Some of these SNPs influence individual characteristics such as appearance, skills, sensitivity to toxins, or certain diseases. One important aim of biomedical research is to identify such SNPs. Because SNPs often have an influence on the functioning of certain genes, important insights can be gained on the molecular processes on which certain individual characteristics are based.

The ENIGMA consortium has now managed to identify 306 SNPs that influence the thickness and surface area of the cerebral cortex. Overall, the influence of SNPs accounts for about one third (34 %) of the population’s variability in the surface area of the cerebral cortex, and about one quarter (26 %) of the differences in its average thickness. “Frequent genetic varieties that every human carries thus make up a significant part in the formation of the human cerebral cortex,” concludes Thomas Mühleisen, biologist in Cichon’s working group.

Finding the influence of genetic factors on structural characteristics of the cerebral cortexFinding the influence of genetic factors on structural characteristics of the cerebral cortex: Differences in the cortical surface area and thickness were measured by means of magnetic resonance imaging in tens of thousands of adults and statistically analysed together with millions of DNA building blocks. The association between two building blocks (SNPs) and two regions is highlighted in red and yellow. Brain scan kindly provided by Tyler Ard, James Stanis, and Arthur Toga from the Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, USA.
Copyright: Tyler Ard, James Stanis, und Arthur Toga vom Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, USA / Forschungszentrum Jülich

“We observed highly significant associations between the individual SNPs and the total surface area of the cerebral cortex,” explains Svenja Caspers, anatomist and working group leader at Forschungszentrum Jülich. She is also in charge of Jülich’s 1000BRAINS study. “There were notable indications that there is a correlation between the total surface area with both the general cognitive function and with the test subject’s level of education,” adds Christiane Jockwitz, psychologist in Caspers’ working group. “In addition, we found correlations between the total surface area and Parkinson’s disease while matching the genetic data of patients,” says Cichon. “However, there is no indication that the disease is caused by it.” SNPs for insomnia, attention deficit hyperactivity disorder (ADHD), depressive symptoms, major depressive disorder, and neuroticism correlate with the total surface area of the cerebral cortex.

The analysis of the functioning and activity of the identified genes suggests that SNPs which have an influence on the surface area of the cerebral cortex are active during the early development of embryos. “In contrast, SNPs that correlate with the average cortical thickness indicate genes that are involved in development processes at later stages of embryogenesis.” These include the branching and the formation and degeneration of synapses as well as the insulating sheath of neurons, also known as myelin .

Considering these results in combination supports the hypothesis that the enlargement of the surface area and the increase in thickness of the cerebral cortex are stimulated by various development mechanisms. “This corresponds to the radial unit model of neural pathway identification,” says Caspers. “The model describes the development of the cortical layers in the human brain by means of special cells in the nervous tissue, called glia cells, which serve as support for nerve cells that move along them and form the layers. No other organ in the human body is formed like this.”

Original paper: The genetic architecture of the human cerebral cortex, by Katrina L. Grasby et al., Science 20 Mar 2020, Vol. 367, Issue 6484, eaay6690, DOI: 10.1126/science.aay6690

Further Information:

Institute of Neuroscience and Medicine, Structural and functional organisation of the brain (INM-1)

Website Genomic Imaging working group

Website Connectivity working group

Website of ENIGMA consortium

Contact:

Prof. Dr. Sven Cichon
Institute of Neuroscience and Medicine
Structural and functional organisation of the brain (INM-1)
Genomic Imaging working group
Tel.: +49 2461 61-6443‬
E-Mail: s.cichon@fz-juelich.de

Prof. Dr. Dr. Svenja Caspers
Institute of Neuroscience and Medicine
Structural and functional organisation of the brain (INM-1)
Connectivity working group
Tel.: +49 2461 61-1742
E-Mail s.caspers@fz-juelich.de

Press contact:

Dr. Regine Panknin
Corporate Communications
E-Mail: r.panknin@fz-juelich.de