Publications

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes

Authors: G. Huguet, T. Renne, C. Poulain, A. Dubuc, K. Kumar, S. Kazem, W. Engchuan, O. Shanta, E. Douard, C. Proulx, J.-L. Martineau, Z. Saci, J. Mollon, L. M. Schultz, E. E. M. Knowles, S. R. Cox, D. Porteous, G. Davies, P. Redmond, S. E. Harris, G. Schumann, G. Dumas, A. Labbe, Z. Pausova, T. Paus, S. W. Scherer, J. Sebat, L. Almasy, D. C. Glahn, S. Jacquemont

The researchers assessed the relationship between copy-number variants (CNVs) and cognitive ability using data from six cohorts, including the CARTaGENE cohort. They performed a genome-wide association study (GWAS) with 258,292 individuals, identifying a duplication at 2q12.3 associated with higher cognitive performance. A functional-burden analysis was developed to examine the association between cognition and CNVs disrupting 6,502 gene sets defined across various biological tissues, cell types, and ontologies. Among these, 864 gene sets were linked to cognition, with the effect sizes of deletions and duplications negatively correlated. Deletions affected subcortical regions and postsynaptic functions, while duplications impacted the cerebral cortex and presynaptic functions.