Educational Attainment Polygenic Scores and School Performance in Adolescents With Psychiatric Disorders: A Population-based Analysis of 86,122 Individuals From the iPSYCH2015 Case-Cohort

Objective: Educational attainment (EA) is a major determinant of well-being and is influenced by genetic and environmental factors. This study investigated whether polygenic scores for EA (EA-PGSs) relate to school performance in adolescents with and without psychiatric disorders and whether associations vary by parental education and sex. Method: We analyzed 86,122 individuals (36,659 with psychiatric disorders) from the Danish iPSYCH2015 case–cohort. Associations between EA-PGSs, psychiatric diagnoses, and ninth-grade examination outcomes (passing rates and Danish and mathematics grades) were assessed using regression models, adjusting for covariates. Results: A higher EA-PGS was associated with lower odds of several psychiatric disorders, including attention-deficit/hyperactivity, attachment, neurotic, oppositional defiant/conduct, and substance use disorders, and intellectual disability. Regardless of case status, individuals with higher EA-PGSs were more likely to pass the examination and achieve higher grades. At comparable EA-PGS values, adolescents with psychiatric disorders performed worse than controls. For pass/fail, EA-PGS effects differed between cases and controls in attachment, eating, neurotic, mood, substance use, and tic disorders and intellectual disability (qFDR < .05), being larger in cases for all groups except intellectual disability, where effects were attenuated. Parental education, but not sex, modified the association between EA-PGSs and passing (interaction p = .008), with differences by parental education evident at lower EA-PGS levels. Conclusion: A higher EA-PGS was associated with better school performance, but adolescents with psychiatric disorders performed worse than controls after accounting for EA-PGSs. Performance differences persisted after accounting for EA-PGSs. Both EA-PGSs and parental education were associated with educational outcomes, indicating that genetic and familial factors are related to variation in school performance.