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New insights into the brain by combining brain scans and DNA profiles

12 September 2023
Our brain and DNA are unique: we all have it, but with slight differences between people. Through Elleke Tissink's research, it is becoming increasingly clear which differences in our DNA are associated with which differences in our brains. For example, she found that common variations in DNA likely affect the volume of the cerebellum, through their impact on brain development. A link also emerged between a genetic susceptibility to depression and the size of multiple brain regions.

Small genetic variations

Our brains are responsible for numerous functions, including our perception, attention, emotions, language and memory. A disorder in the brain, or brain disease, can cause symptoms in these functions. A brain disease is not caused by just one gene but often arises from an interplay between environmental influences and heredity. Heredity is not caused by just one gene but often involves hundreds of genes. The influence of heredity can be measured by mapping countless small genetic variations.  Numerous variations are possible for each genetic trait. The difference in such a variation is just one building block that is slightly different. You can compare this to a necklace of beads. For example, if you have four white beads and then one colored bead, everyone's colored bead could be a different color; red or green. These small genetic variations occur in every human being. But, what exactly does it mean if you have a red bead or just a green bead in your personal bead necklace? Does the red bead cause the brain structure to be larger or smaller in that particular spot in the brain? And how is a small genetic variation related to the rest of all your personal building blocks and possible brain diseases? That's what Tissink has been researching.

Different genetic links

Through the unique combination of brain scans and DNA profiles, efforts have been made to map the biological workings of the brain even better. Tissink's research revealed several leads by mapping different genes, the function and location of these genes, as well as the strength of the effect they have on both brain structure and brain function when something is wrong with these genes. The latter is important for getting a good picture of brain diseases. For example, a link has been found between Alzheimer's disease and a known brain network (multiple brain regions working together) involved in, for example, converting short-term to long-term memory, also called memory consolidation.

Treasure of information from database

But, not only brain diseases were looked at in the study. Differences in the healthy brain, such as the size of the cerebellum, for example, could also be linked to genetic variations through this research. Or how strong the cooperation of different brain regions is within an individual's brain and how the difference in cooperation can in turn be linked to different psychiatric disorders. Combining brain scans and DNA profiles as done here by Tissink would have been impossible just a few years ago. But, because 40,000 people had brain scans and also donated their DNA in the United Kingdom, a huge database was built up. This made it possible for the first time to be able to link an individual's genetic profile (the personal bead necklaces) to the corresponding brain scan of that same individual. In the future, as many as 100,000 brain scans and DNA profiles are expected to become available for scientific research.

"Using sophisticated models, the areas on the brain scans were automatically labeled and measured. In addition, we were able to filter out from the DNA profiles the locations where the genetic code differs slightly between people" explains the researcher.And in this way, a link can be made between common variations in DNA and the brains of all these people.Because of her research, follow-up research can again be conducted so that in the future we can even better determine how our DNA and brain properties can be linked to brain diseases.

Tissink PhD defence is 22 September at Vrije Universiteit Amsterdam

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