The genetic architecture of language functional connectivity
© NeuroSpin/CEA. Figure legend: The genetic architecture of language functional connectivity A) Twenty-five ROIs from meta-analysis (Vigneau et al. 2006 and 2011) B) 142 heritable averaged FC C) Manhattan plot from MOSTest D) Perceptual-motor interaction associated with rs1440802 (THBS1), LocusZoom, BrainSpan gene expression data, effect sizes of variants. E) Fronto-parieto-temporal semantic network associated with rs35124509 (EPHA3), LocusZoom, BrainSpan gene expression data, effect sizes of variants.
In the present study, to analyse the genetic architecture of language functional connectivity, researchers performed a genome-wide multivariate association analysis between genetic variations and resting-state functional connectivity of 25 classic language brain areas, extracted from a meta-analysis of 129 fMRI studies of language tasks, in 32,186 participants from the UK Biobank. Three hundred FCs were calculated between all pairs of the regions considered. Of these, 142 were found to be significantly heritable and were included in the subsequent multivariate association study. Twenty genomic loci were found to be associated with language FC. Among them, the EPHA3 gene, putatively involved in dyspraxia, dyslexia and specific language impairment, was found to be associated with the fronto-parieto-temporal semantic network. The THBS1 gene, involved in synaptogenesis, proliferation and differentiation of neural progenitor cells is associated with the perceptual-motor interaction required for language. Finally, the PLCE1 gene has a potential role in the bilateral frontotemporal auditory-motor network.
Using a multivariate approach, the researchers studied language using data from the largest imaging-genetics cohort to date, without language-related cognitive scores or language-oriented fMRI tasks. They identified potential key language-related genes that could provide new insights into the neurobiology of this complex process.
Functional connectivities (FC) represent correlations between the average fMRI signals of the regions under consideration.
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- Département de Biologie Computationnelle, Institut Pasteur ;
- Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CEA - CNRS - Université de Bordeaux ;
- Basque Center on Cognition, Brain and Language, San Sebastian, Spain
Yasmina Mekki , Vincent Guillemot , Herve Lemaitre, Amaia Carrion-Castillo, Stephanie Forkel, Vincent Frouin, Cathy Philippe. The genetic architecture of language functional connectivity. Neuroimage, vol 249 2022 https://doi.org/10.1016/j.neuroimage.2021.118795