Genetics of aggression and brain white matter structure

Hyun investigated the genetics of aggression-related phenotypes, using data from NeuroIMAGE. In addition he also studied gene-environment interactions (GxE) and brain white matter structure. The research that Hyun conducted using data from NeuroIMAGE was part of his PhD project and the aggression-focused EU MATRICS-consortium.
Aggression is a heritable trait, with estimates of up to 50% heritability. Because aggression constitutes a heterogenous phenotype, with different perspectives to subtyping – e.g. proactive versus reactive aggression – and overlap with different kinds of disruptive behavior – e.g. conduct problems and callous-unemotional traits – Hyun was interested in investigating the genetics of aggression in more detail. To this end, he performed polygenic risk score analyses, using summary statistics from the largest available pediatric genome-wide association study (GWAS) of aggression (by Pappa et al., 2016) and used the individual-level genotype and phenotypic data from NeuroIMAGE. He observed evidence pointing to a shared genetic etiology between aggression as a more general trait among children in the population and certain aspects of callous-unemotional traits in the children of NeuroIMAGE (constituting a sample enriched for ADHD). In addition to a shared genetic etiology as such, Hyun also confirmed genetic sharing within certain pathways, namely glutamatergic, dopaminergic and neuroendocrine signaling. Furthermore, a GxE interaction involving aggression polygenic risk scores and stress resulting from negative life events during childhood/adolescence in relation to callous-unemotional traits was observed.
Because previous studies have implicated a range of brain white matter tracts in relation to aggression-related phenotypes, Hyun also studied whether genetic liability for aggression might be related to the brain’s white matter structure. Results indicate that such genetic liability for aggression (i.e. polygenic risk scores for aggression) could be linked to measures of brain white matter structure.