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

Abstract 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 (PRSMDD) and for educational attainment (PRSEDU). 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 PRSMDD 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 PRSEDU 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 PRSMDD and PRSEDU on self-harm risk were strongest for individuals with poor school performance. Conclusion Associations between PRSMDD and self-harm risk and between PRSEDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

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