Estimating developmental changes within the genetic architecture of social communication traits: A multivariate study of genetic variance in unrelated individuals

Background: Social-communication problems are heritable traits that share genetic influences with multiple psychiatric conditions, as tagged by common variants. The degree of trait-disorder overlap depends, however, on the... [ view full abstract ]

Background: Social-communication problems are heritable traits that share genetic influences with multiple psychiatric conditions, as tagged by common variants. The degree of trait-disorder overlap depends, however, on the developmental stage of the behaviour studied. This suggests changes in the genetic trait architecture that are part of human maturation processes. We developed a multivariate analysis framework in unrelated individuals to assess the developmental profile of genetic influences contributing to social-communication difficulties during a ~10-year period spanning childhood and adolescence.

Methods: Standardised longitudinally assessed quantitative social-communication problems (N≤ 5,551, Social Communication Disorders Checklist, 8 to 17 years) were studied in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort. Genetic influences across development were investigated using multivariate genetic-relationship-matrix structural equation models (GSEM). This analysis combines whole-genome genotyping information with structural equation modelling techniques. Analogous to twin research, GSEM included a Cholesky decomposition model, a common pathway model and an independent pathway model.
 
Results: A Cholesky decomposition model, specifying two distinct genetic factors arising during childhood, fitted the data best. One genetic factor was common to SCDC measures across development (path coefficients: 0.20 (S.E.=0.07) to 0.54 (S.E.=0.07)). The other factor accounted for independent phenotypic variation at 11 and 17 years of age (path coefficients: 0.20 to 0.44). Genetic factors operating at age 8 years explained ~60% (S.E.=0.13) of genetic variation at age 17 years.
 
Conclusion: We identified dynamic changes in genetic factors influencing social-communication difficulties during child and adolescent development, consistent with distinct developmental trait profiles in genetic overlap with psychiatric illness. Our findings have relevance for studies investigating shared genetic aetiologies across multiple phenotypes.