Unique prediction of developmental psychopathology from genetic and familial risk

Early detection is critical for easing the rising burden of psychiatric disorders. However, the specificity of psychopathological measurements and genetic predictors is unclear among youth.

We measured associations between genetic risk for psychopathology (polygenic risk scores (PRS) and family history (FH) measures) and a wide range of behavioral measures in a large sample (n = 5,204) of early adolescent participants (9-11 years) from the Adolescent Brain and Cognitive Development Study^SM . Associations were measured both with and without accounting for shared variance across measures of genetic risk.

When controlling for genetic risk for other psychiatric disorders, polygenic risk for problematic opioid use (POU) is uniquely associated with lower behavioral inhibition. Attention deficit hyperactivity disorder (ADHD), depression (DEP), and attempted suicide (SUIC) PRS shared many significant associations with externalizing, internalizing, and psychosis-related behaviors. However, when accounting for all measures of genetic and familial risk, these PRS also showed clear, unique patterns of association. Polygenic risk for ASD, BIP, and SCZ, and attempted suicide uniquely predicted variability in cognitive performance. FH accounted for unique variability in behavior above and beyond PRS and vice versa, with FH measures explaining a greater proportion of unique variability compared to the PRS.

Our results indicate that, among youth, many behaviors show shared genetic influences; however, there is also specificity in the profile of emerging psychopathologies for individuals with high genetic risk for particular disorders. This may be useful for quantifying early, differential risk for psychopathology in development.