The triple burden of mental illness? A sibling analysis of parental education, polygenic scores, and gene–environment interactions

This study examines whether parental socioeconomic resources and polygenic risk jointly shape mental health among siblings. Utilizing Finnish population registers linked to polygenic scores (PGSs), we analyze 21,178 sibling pairs (50.5% female and median year of birth 1961). We first assess whether PGSs for mental illness differ by parental education. Second, we test the polygenic prediction of psychiatric diagnoses and psychotropic medication use applying the recently developed phenotype differences model, which estimates direct genetic effects free from environmental confounding and requires genotyping of only one sibling. Third, we assess whether the relationship between polygenic risk and mental illness varies by parental education. Group differences in the PGSs were minimal. In within-family analyses, we found direct genetic effects in 7 of 12 outcome-PGS combinations. Results are contrasted with between-family analyses of unrelated individuals. Evidence that parental education moderates polygenic risk was weak and did not hold up under stringent statistical tests, highlighting challenges detecting gene-environment interactions in mental illness.