The genetic code of memory: searching for the building blocks of recall
Human memory is one of biology’s most intriguing puzzles. We believe it is made up of different types, short-term, long-term, visual, and textual, but pinning down its precise genetic foundations remains like searching for a needle in a haystack. Researcher Daan van Beek delved into the data of healthy American volunteers, stretched the boundaries of statistical analysis, and pointed towards a direction in that haystack.
Daan van Beek stumbled into memory genetics research by chance. “My interest lies in large genetic datasets for unravelling the underlying processes of various conditions, from heart disease to brain function,” he explains. His focus on memory emerged during his master’s thesis, when he signed up for a project at the Maastricht Centre for Systems Biology and Bioinformatics (MaCSBio). “I’ve always been fascinated by brain biology, but it wasn’t an intentional choice to specialise in memory.” After graduating, he stayed on at MaCSBio, where new questions and improvements in the research kept him engaged. “Eventually, a coherent story began to take shape.”
What was already known?
Memory is not a single entity but a collection of different systems in the brain. Psychologists distinguish between short-term, long-term, visual, numerical, and textual memory, among others. “But we don’t know if these types are genetically distinct,” says Daan. “Up until now, genetic studies have often focused on just one subtype, such as visual memory. We wanted to find out which groups of genes are associated with the various types of memory.”
A unique dataset
Daan and his colleagues analysed data from Americans aged 22 to 35, with no learning disabilities or dementia. The data came from Washington University’s Human Connectome Project, where participants underwent extensive memory tests, MRI scans, and genetic analyses. “This dataset is somewhat unique because we could compare different types of memory within the same group, with lifestyle factors and brain scans also available.”
The choice of young, healthy individuals was deliberate. “Many memory studies look at older people with or without dementia or compare young and old people. In those cases, you’re mainly looking at what goes wrong in disease,” Daan explains. “We wanted to know: what is genetically different between healthy people without obvious problems?”
What did Daan discover?
The research confirmed what was already suspected: there is no single ‘memory gene’. Instead, hundreds of genes play a role, each with a small effect. “Some genes code for proteins involved in communication between neurons and others in immune processes in the brain,” says Daan. “Stress, for example, could trigger immune reactions that affect brain function.”
The researchers also found evidence that certain biological processes, or ‘pathways’, are involved in different types of memory. “People with schizophrenia often have problems with verbal and visual memory. In our data, we saw overlap between genes linked to schizophrenia and to verbal memory. This suggests there are indeed biological connections.”
Statistical rules adjusted
To uncover these complex links, Daan adjusted the rules of statistics. Normally, researchers use a p-value of 0.05, meaning there is at most a 5% chance that a result could be found by chance. “But if you test thousands of genetic variants, that p-value becomes so small that the test is too strict to find anything,” he says. “We relaxed that threshold. This allowed us to identify groups of genes that work together in the same pathways.”
Better hunches
Daan is cautious about drawing firm conclusions. “The results may not be statistically significant by the usual standards, but they do point us in a direction for further research.” He isn’t ready to bet everything on the genes and pathways they’ve identified. “But if other research points in a similar direction, such as with schizophrenia, the evidence becomes stronger. Those genes and pathways seem more likely to be genuinely involved in memory.”
The needle in the haystack
Daan’s research is a step forward, but the search for the needle in the haystack continues. “We now have a better idea of where the needle might be,” he says. “But the complex interplay between genes, brain regions, and environmental factors remains a mystery for now.” The hope is that future research, with even larger datasets and better techniques, will bring us closer to the answer. “Perhaps one day we’ll be able to precisely predict which genes in which brain regions play a role in different types of memory. For now, the search goes on.”
Text: Patrick Marx
