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Relating genetic variation to brain volume

How does the gene CNTNAP2 relate to structural variations in the brain? In our new publication, in press in Brain and Language, we looked at the association between a CNTNAP2 variant and grey matter volume in a large group of more than 1700 subjects. We found associations of CNTNAP2 with grey matter in a region in the left superior occipital gyrus, while earlier reported associations in other brain regions were not replicated.
Relating genetic variation to brain volume

The human genome makes for a language-ready brain. The most well studied gene that has been implicated in communicative and linguistic traits is FOXP2. This gene regulates multiple other genes involved in neural connectivity and plasticity. One of these targets is the gene encoding contactin-associated protein-like 2 (CNTNAP2, pronounced as ‘cat-nap-two’). This gene encodes a cell-adhesion molecule that influences the properties of neural networks. Previous studies have related genetic variation in CNTNAP2 to individual differences in language, both in the healthy population and in developmental disorders. Also, different neuroimaging studies have found associations between CNTNAP2 variants and the neural response to language. However, none of these findings have been independently replicated.

In this new study we set out to replicate an earlier study by Tan and colleagues (2010) that reported associations between a common CNTNAP2 variant and structural brain properties in nine brain areas. We compared gray matter volume in these regions in a large group of 1717 subjects. We replicated the association between the CNTNAP2 variant and grey matter volume in one of the regions only, left superior occipital gyrus.

With this study we again want to stress the importance of independent replication in neuroimaging studies of language-related candidate genes. Our results suggest that common genetic variation in CNTNAP2 is related to individual differences in brain structure in the visual dorsal stream, highlighting the complexity of relationships between genes, neurons, circuits and cognitive processing.  


Uddén, J., Snijders, T.M., Fisher, S.E., Hagoort, P. (2017). A common variant of the CNTNAP2 gene is associated with structural variation in the left superior occipital gyrus. Brain and Language, 172, 16-21.

Neurobiology of Language

What is the neurobiological infrastructure for the uniquely human capacity for language? The focus of the Neurobiology of Language Department is on the study of language production, language comprehension, and language acquisition from a cognitive neuroscience perspective. Read more...

Director: Peter Hagoort

Secretary: Carolin Lorenz


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