Polygenic score prediction of psychopathology dimensions and diagnoses within and between families

The population prediction of polygenic scores (PGS) was found to capture two distinct processes: within-family prediction (individual-specific genetic differences between family members, such as siblings) and between-family prediction (family-level genetic differences, including assortative mating and ancestry). We quantify between-family prediction as the extent to which population prediction exceeds within-family prediction. While between-family prediction was found to be substantial for cognitive traits, its magnitude for psychopathology remains underexplored. Using 3300 unrelated individuals and 1600 dizygotic twin pairs at age 26 in the UK-based Twins Early Development Study, we examined within-family and population-level PGS prediction for eight psychopathologies, assessed as dimensions and diagnoses. Despite limited statistical power, within-family prediction is broadly comparable to population prediction, accounting for 72.4% of population estimates for dimensions and 78.0% for diagnoses. Only anxiety dimensions showed a significant prediction difference, suggesting some between-family contributions. We conclude that, overall, population PGS for psychopathology primarily reflect within-family genetic effects.