Impaired executive function (EF) is associated with increased risk of psychopathology and lower academic achievement. However, relatively little is known about the genetic architecture of EF traits, and the pathways linking... [ view full abstract ]
Impaired executive function (EF) is associated with increased risk of psychopathology and lower academic achievement. However, relatively little is known about the genetic architecture of EF traits, and the pathways linking genes, cognitive processes and later academic and mental health outcomes. We previously characterized three latent cognitive variables in an adolescent sample; two EF traits (working memory and inhibitory control) and processing speed. We found that each trait explained differing unique variance in maths, English and science as well as DSM V assessments, suggesting that in order to understand specificity in academic and psychological outcomes, an understanding of individual differences at a neurocognitive level is necessary. The goal of the present study was to add to current understanding of the genetics of EF in adolescence and their genetic relationship to psychological and academic outcomes.
We performed univariate genome-wide association studies (GWAS) for working memory, inhibition and processing speed (N=4,817) with adolescents from the Avon Longitudinal Study for Parents and Children. Linkage disequilibrium (LD) score regression was used to estimate the heritability of each trait as well as genetic correlations between our traits and measures of attainment, IQ and psychopathology.
A moderate SNP-based heritability estimate was found for WM (0.25) with a smaller estimate for processing speed and IC. Uniformly high (0.66-1.00) genetic correlations were observed for WM and intelligence and educational traits. Moderate to high correlations were found with Anorexia, Depressive Symptoms and ADHD.
The picture was more varied for processing speed, as with IC, possibly due to the large standard errors for their heritability estimates. Univariate GWA analyses failed to detect any genome-wide significant associations. However, 50 lead single nucleotide polymorphisms (SNPs) reached suggestive significance, 15 of which are located in genes previously implicated in GWA studies of education, cognition or psychopathology. MAGMA gene analysis showed there to be a higher representation of genes expressed in the brain for WM but not the other traits. The results suggest that WM is highly polygenic trait with links to risk for specific psychopathologies. However it was not clear that studying EF traits is more powerful that studying the end phenotypes themselves.
