Executive functions (EFs) are top-down cognitive control mechanisms that direct goalorientated behaviors. EF deficits are associated with psychopathology and neurological disorders, but little is known about the molecular bases of EF individual differences. Existing genome-wide association studies (GWAS) of EFs used small sample sizes and/or individual tasks, which are mixtures of higher and lower order cognitive mechanisms. To remedy these limitations, we conducted a GWAS of a "Common EF" (cEF) factor based on multiple tasks in the UK Biobank (N=93,027-427,037), finding 299 independent loci. Gene-based analysis found synaptic, potassium channel and GABA pathways associated with cEF. cEF genetically correlated with almost all psychiatric traits and with behavioral and health outcomes. These patterns of genetic correlations were different than those previously found for intelligence. Our results suggest that cEF is neurologically complex and that fast-neuronal processes form a basis for genetically influenced cognitive outcomes in health and psychiatric dysfunction.
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