School performance and genetic propensities for educational attainment and depression in the etiology of self-harm: a Danish population-based study

Background: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRS_MDD) and for educational attainment (PRS_EDU). Method: We conducted a follow-up study of individuals born 1987–98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers. Results: Individuals in the top PRS_MDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15–1.46), whereas individuals in the top PRS_EDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55–0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44–1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47–15.18). Observed effects of PRS_MDD and PRS_EDU on self-harm risk were strongest for individuals with poor school performance. Conclusion: Associations between PRS_MDD and self-harm risk and between PRS_EDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.