General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

Abstract

Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy individuals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the general cognitive ability (g). However, there is an ongoing debate whether executive functioning (EF)–another key predictor of cognitive health and performance, is separable from general g. To provide an analytical review on existing findings on genetic influences on the relationship between g and EF, we re-analysed a subset of genome-wide association studies (GWAS) from the GWAS catalogue that used measures of g and EF as outcomes in non-clinical populations. We identified two sets of single nucleotide polymorphisms (SNPs) associated with g (1,372 SNPs across 12 studies), and EF (300 SNPs across 5 studies) at p<5x10-6. A comparative analysis of GWAS-identified g and EF SNPs in high linkage disequilibrium (LD), followed by pathway enrichment analyses suggest that g and EF are overlapping but separable at genetic variant and molecular pathway levels, however more evidence is required to characterize the genetic overlap/distinction between the two constructs. While not without limitations, these findings may have implications for navigating further research towards translatable genetic findings for cognitive remediation, enhancement, and augmentation.

Intelligence, cognition, and major neurocognitive disorders: From constructs to measures

“…A recent meta-analysis of studies on the relationships between the Wisconsin Card Sorting Test and intelligence found that overall shared variance was modest and just one third of the test variability could be accounted for by variability in common indicators of intelligence [31] . Studies on the genetic associations between executive functions and general intelligence suggest that they are overlapping but separable at genetic variant and molecular pathway levels, and that in adulthood, common EF abilities are distinct from intelligence that otherwise seems associated with working memory updating-specific EF abilities [ 32 , 33 ]. Overall, research has demonstrated that executive functions only partially correspond to the psychometric concept of intelligence, and their relationship is a controversial issue.…”