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

PLoS One. 2022 Oct 17;17(10):e0272368. doi: 10.1371/journal.pone.0272368. eCollection 2022.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Executive Function*
  • Genome-Wide Association Study
  • Humans
  • Intelligence* / genetics
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide

Grants and funding

L.G.C. contribution was funded by the Australian Army Headquarters (AHQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.