Scanning the crowd for intelligence.

CNCR researcher Danielle Posthuma, in collaboration with Peter Hagoort and Guillén Fernandez (FC Donders Centre Nijmegen), won a NWO Open Competition grant with a proposal that aims to integrate neurogenetics with the field of neuroimaging. This will improve her understanding of the interaction between intellectual functioning and the genetic make-up of an individual. 

'We know that genes dictate human intelligence, at least for a substantial part, and especially in adults. But that observation does not bring us too much further to understanding why this is the case. We have little insight in for example which genes are important in determining intelligence, and in the small number of cases that are known we do not understand how those genes influence brain function. There are many steps between the genes and a performance on a cognitive test, ranging from the transcription, the proteins that are formed in the neuronal cells and how these cells are interconnected to form neural networks. We want to look at that route in an integrative way.'

A collaboration with the F.C. Donders institute for Brain, Cognition and Behaviour in Nijmegen has to bring the expertise to make the translation from genes to real-time cognitive function. For the NWO grant Posthuma worked together with professor Peter Hagoort and professor Guillén Fernandez, both renowned scientists in the field of neuroimaging and functional MRI studies. Together they will use the NWO funding to hire a PhD student that will connect the imaging specialists in Nijmegen with the extensive experience in neurogenetics at the CNCR in Amsterdam. Posthuma: 'We have a database available that includes 1200 subjects with structural MRI data of the brain as well as DNA of those individuals. One of our first investigations will be whether genes previously associated with intelligence are associated with the volume of specific areas of the brain which are thought to be important for intelligence. In a later phase of the project we want to specifically screen for genetic impact on the way the brain works, using functional MRI studies during the execution of tests that can measure intelligence.'

Danielle Posthuma feels a strong drive to unravel the mechanisms that underlie both brain function and cognitive disease. After graduating in both medical antropology and physiological psychology she worked on the genetic causes of cognitive dysfunction during her PhD project. Her thesis research forced her to thoroughly re-think her methods of data analysis and statistics, and she has been focussing on innovative ways to process the complex data that is yielded by the genetic association studies ever since. Collaborating with Peter Visscher (University of Queensland, Australia) who holds a visiting professorship at the CNCR she successfully develops new strategies to dissect the interactions of gene sets, aiming to identify gene networks that influence cognitive function.

'We recently applied a gene network approach to intelligence, as well as several mental disease. Genes that are part of the same network have a complementary function, which explains why single variant genes often have no direct effect on brain function: unless the whole network is disrupted the other genes can compensate for dysfunction of individual genes, up to some point of course. Thus, we want to link these gene networks to brain function, as well as a short list of other individual genes which we think are involved in cognitive processes.'

Posthuma is convinced of the profound impact of the genes and gene-environment interaction on intelligence. 'Twin studies learn us that genetics predict approximately sixty to eighty percent of the intelligence in adults. In children that figure is way lower: at the age of five for example heredity of IQ hovers around thirty percent. But as people grow up and move out the genetic component becomes more important. This is a strong indication that the environment that people choose is a function of their genetic make-up.'

The new project forms an important branch of Posthuma's research, extending her work towards brain function in humans.  'The good part about this project is that we do not restrain ourselves to the identification of new genes involved in intelligence, but we also want to understand how these genes affect brain function. We aim to improve our knowledge about the way that the genetic background of an individual leads to quantifiable neurobiological effects, in this case intellectual functioning.'

Lucas Maillette de Buy Wenninger