Disentangling multivariate relationships between cognition, language and social traits: structures of G, E, and r G E

Cognitive, language, and social abilities are complex, heritable and intertwined traits shaping children's development and later mental health. To better understand cross-trait interrelationships, we model here the structures of shared genomic and shared non-genomic/residual (i.e. broadly environmental) influences, and their correlation ( $r_{GE}$ ), investigating cognitive, language, and social behavioural/communication measures.

Data were obtained for unrelated children (8-13 years) from two population-based cohorts: the UK Avon Longitudinal Study of Parents and Children (ALSPAC, N≤6,543) and the US Adolescent Brain Cognitive Development^℠ (ABCD) Study (N≤4,412), and analyses were carried out implementing an extended data-driven genetic-relationship-matrix structural equation modelling (GRM-SEM) approach.

In ALSPAC, we identified two independent phenotypic domains, each captured by a structurally matching pair consisting of a genomic (A) and a non-genomic/residual (E) factor. The first domain reflected cognitive/language difficulties, with the largest genomic and residual factor loadings ( ${\lambda }_A$ and ${\lambda }_E$ , respectively) for verbal IQ ( ${\lambda }_A=0.73(SE=0.05)$ ; ${\lambda }_E=0.57(SE=0.07)$ ). The second domain captured social difficulties, with the largest ${\lambda }_A$ and ${\lambda }_E$ for social communication measures ( ${\lambda }_A=0.39(SE=0.10)$ ; ${\lambda }_E=0.82(SE=0.10)$ ). We identified trait-specific $r_{GE}$ between pairs of A and E factors with different directions of effect (cognition/language $r_{GE}=0.89(SE=0.18)$ , social $r_{GE}=-0.62(SE=0.17)$ ). $r_{GE}$ patterns were linked to increased measurable A and E contributions for cognition/language difficulties, but decreased contributions for social problems. Analyses in ABCD confirmed the two domains for E and phenotypic structures, although genomic contributions were low.

In childhood, cognitive/language abilities versus social abilities are influenced by distinct genomic and/or environmental factors, potentially interlinked through trait-specific $r_{GE}$ , suggesting differences in developmental processes.