GENE Amsterdam Interview Session 4: Dennis van ‘t Ent

This month, we interview Dennis van ‘t Ent: associate professor at the department of Biological Psychology at the Vrije Universiteit Amsterdam

Please tell us about your background and how you became an imaging genetics researcher.

I studied physics and astronomy, but I’ve always had an interest in medicine. During the end of my physics studies, I specialized in medical physics and did an internship that involved human studies. I started by doing eye-movement recordings because they are an important window into the brain. After the internship, I did a PhD in Rotterdam on EEG recordings, with a focus on cognition. After that, I returned to Amsterdam to do a postdoc at the VU Medical Center, where I worked at the center for magnetoencephalography, which was a relatively new technique back then. I currently work as an associate professor at the Netherlands Twin Register at the VU, where I teach a lot and focus again on neuroimaging now mainly using MRI scans. 

For those in our audience who may be less familiar with imaging genetics, could you explain the basics of this field?

Imaging genetics can be broadly defined as the study of how genes influence our brains. On the one hand, we want to know what genes are relevant and how they affect the brain, and on the other hand, we are interested in the effect on behavior. So we are looking from genes to the brain, to behavior. Besides the genetic contribution, the environment also plays a large role in shaping both the brain and behavior. With twin data, we can tease out the genetic and environmental contributions. 

In genetic research, large samples are required to find robust effects. Do you need similar sample sizes for imaging genetics and how attainable is it to get such large samples with MRI data?

Imaging genetics generally also needs large sample sizes, although the exact number depends on multiple factors. Older studies used to have smaller samples, but recent research has shown that we do need larger samples for reliable findings. One way to accommodate this is to form large consortia, such as ENIGMA, that pool MRI data from many labs, which has been an important development in the field. We can also make use of large biobanks like the UK Biobank. However, the required sample size depends on the trait you are investigating. It has been shown that for some variables, such as adult age, you need at least 300 people to see an effect related to the brain, but for other traits, you need more than thousands of individuals. It furthermore depends on which brain area you are looking at, as effect sizes can be larger for some than for other regions. Additionally, if you only focus on one region, you will also have a lower multiple comparison problem, in which case you would need fewer individuals. 

Is the field theory-driven then, if you can preselect certain brain regions? 

It depends on the research question. The whole brain is often included, but if you are interested in for instance executive function, you may focus on the frontal lobe. For emotion, you may study the amygdala. 

Are brain imaging traits mediating the effects of variants on traits? Can they provide more insight into biology?

Yes, but this again really depends on the trait you look at. Take substance abuse for instance, where you may expect that genes affect the development of the reward system in the brain, such that you are more sensitive to substance use. But there is also the issue of reverse causality, where people who have a genetic predisposition for substance use will use alcohol or smoke frequently, which in turn affects the brain. We need to tease those effects apart. This is difficult of course, but longitudinal or Mendelian Randomization studies may be useful here. 

You are a member of the GENE Amsterdam Scientific Outreach Committee, can you tell us what this committee is currently doing?

We are involved in providing news content on the GENE amsterdam website and social media and we are also working to obtain funding for our activities. We are currently preparing a funding proposal for outreach to high school students in the Netherlands about genetics and its relationship to society.  

You do a lot of teaching, what do you like most about it?

There are many things. But what I enjoy the most is the interaction with the students and getting them motivated. For example, I teach biological psychology and some of my students have limited backgrounds in biology and have low expectations of the course. But often they become very enthusiastic during the course; it feels good having played a role in that.

Is it difficult to combine teaching with research?

Yes, time is always an issue. I teach in blocks, and in some months there’s barely any time for research at all. That can be very frustrating, as the science never stops. On the other hand, teaching is very important and should not always take the second rank to research activities. One of a university’s main goals is to deliver teaching. It feels like this has been forgotten for a long time and therefore I think the recognition and rewards initiative at universities system is such an important development.

Do you have any favorite brain regions?

Oh, difficult question. It’d probably be the frontal lobe, as it’s related to my PhD work on action monitoring. It’s like the control center of the brain. 

If you weren’t a geneticist, what other field might you have pursued and why?

I would very much have liked to be the goalkeeper of Ajax Amsterdam. But to be more realistic, I am fascinated by the laws of physics and observing them in the universe – a remnant passion from my time studying astronomy. I could have seen myself being an astronomer in the deserts of Chile, looking up at the sky and doing calculations on the stars and the orbits of the planets.. 

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