TY - JOUR T1 - Genetic Variants of <em>FOXP2</em> and <em>KIAA0319/TTRAP/THEM2</em> Locus Are Associated with Altered Brain Activation in Distinct Language-Related Regions JF - The Journal of Neuroscience JO - J. Neurosci. SP - 817 LP - 825 DO - 10.1523/JNEUROSCI.5996-10.2012 VL - 32 IS - 3 AU - Philippe Pinel AU - Fabien Fauchereau AU - Antonio Moreno AU - Alexis Barbot AU - Mark Lathrop AU - Diana Zelenika AU - Denis Le Bihan AU - Jean-Baptiste Poline AU - Thomas Bourgeron AU - Stanislas Dehaene Y1 - 2012/01/18 UR - http://www.jneurosci.org/content/32/3/817.abstract N2 - Recent advances have been made in the genetics of two human communication skills: speaking and reading. Mutations of the FOXP2 gene cause a severe form of language impairment and orofacial dyspraxia, while single-nucleotide polymorphisms (SNPs) located within a KIAA0319/TTRAP/THEM2 gene cluster and affecting the KIAA0319 gene expression are associated with reading disability. Neuroimaging studies of clinical populations point to partially distinct cerebral bases for language and reading impairments. However, alteration of FOXP2 and KIAA0319/TTRAP/THEM2 polymorphisms on typically developed language networks has never been explored. Here, we genotyped and scanned 94 healthy subjects using fMRI during a reading task. We studied the correlation of genetic polymorphisms with interindividual variability in brain activation and functional asymmetry in frontal and temporal cortices. In FOXP2, SNPs rs6980093 and rs7799109 were associated with variations of activation in the left frontal cortex. In the KIAA0319/TTRAP/THEM2 locus, rs17243157 was associated with asymmetry in functional activation of the superior temporal sulcus (STS). Interestingly, healthy subjects bearing the KIAA0319/TTRAP/THEM2 variants previously identified as enhancing the risk of dyslexia showed a reduced left-hemispheric asymmetry of the STS. Our results confirm that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. The observed cortical effects mirror previous fMRI results in developmental language and reading disorders, and suggest that a continuum may exist between these pathologies and normal interindividual variability. ER -