Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition: a multivariable Mendelian randomization study with more than 815,000 participants

Background Rates of suicidal ideation, attempts and completions are increasing and identifying causal risk factors continues to be a public health priority. Observational literature has shown that educational attainment (EA) and cognitive performance (CP) can influence suicide attempt risk; however, due to residual confounding and reverse causation, the causal nature of these relationships is unknown. Methods We perform a multivariable two-sample Mendelian randomization (MR) analysis to disentangle the effects of EA and CP on suicide attempt risk. We use summary statistics from recent genome-wide association studies (GWAS) of EA, CP, household income versus suicide attempt risk in individuals with and without mental disorders, with more than 815,000 combined study participants. Results We found evidence that both EA and CP significantly reduced the risk of suicide attempt when considered separately in single variable MR (SVMR) (Model 1 EA odds ratio (OR), 0.524, 95% CI, 0.412-0.666, P = 1.07⨯10 −7 ; CP OR, 0.714, 95% CI, 0.577-0.885, P = 0.002). When simultaneously analyzing EA,CA, and adjusting for household income but not comorbid mental disorders (Model 1), we found evidence that the direct effect of EA, independent of CP, on suicide attempt risk was greater than the total effect estimated by SVMR, with EA, independent of CP, significantly reducing the risk of suicide attempt by almost 66% (95% CI, 43%-79%); however, the effect of CP was no longer significant independent of EA (Model 1 EA OR, 0.342, 95% CI, 0.206-0.568, P = 1.61×10 −4 ; CP OR, 1.182, 95% CI, 0.842-1.659, P = 0.333). Further, when accounting for comorbid mental disorders (Model 2), these results did not significantly change: we found EA significantly reduced the risk of suicide attempt by 55% (35%-68%), a lower point estimate but still within the 95% confidence interval of Model 1; the effect of CP was still not significant (Model 2 EA OR, 0.450, 95% CI, 0.314-0.644, P < 1.00×10 −4 ; CP OR, 1.143, 95% CI, 0.803-1.627, P = 0.475). Conclusions Our results show that even after accounting for comorbid mental disorders and adjusting for household income, EA, but not CP, is a causal risk factor in suicide attempt. These findings could have important implications for health policy and prevention programs aimed at reducing the increasing rates of suicide.