Risk of non-fatal suicide attempt in individuals with substance use disorder: the roles of aggregate genetic liability and environmental exposures in a Swedish population-based cohort

Abstract

Background and Aims: Substance use disorder (SUD) is related to widespread adverse consequences, including higher suicidality. Shared genetic liability has been demonstrated between SUD and suicidality. Here, we measured the factors that contribute to increased risk of non-fatal suicide attempt among individuals with SUD by focusing upon aggregate genetic risks and both childhood and past-year environmental factors. Design: Longitudinal study. Family genetic risk scores and environmental factors (childhood, aged from 0 to 15 years, and the year preceding SUD registration) were used to predict the relative risk of non-fatal suicide attempt using Cox proportional hazards models. Additional analyses employed a co-relative design, accounting for genetic factors and shared familial environment, to test for potential causality. Setting and participants: Based on longitudinal Swedish registry data, 228 617 individuals with SUD registrations from 1991 to 2015 were included. Measurements: SUD and suicide attempts were identified using medical records (International Classification of Diseases codes). SUD was also identified using pharmacy and criminal registries. Findings: In multivariable analyses that jointly accounted for all the selected potential predictors, individuals with SUD were at higher risk for non-fatal suicide attempt if they had experienced a parental death [hazard ratio (HR) = 1.58; 95% confidence interval (CI) = 1.30, 1.93], were female (HR = 1.53, 95% CI = 1.49, 1.57), had low educational attainment (HR = 1.50, 95% CI = 1.46, 1.55), received social welfare (HR = 1.21, 95% CI = 1.17, 1.25) or had lived in a non-intact family (HR = 1.11, 95% CI = 1.08, 1.14). In co-relative analyses, low education was supported as a possible causal factor for suicide attempt. Aggregate genetic risks interacted with low education and being raised in a non-intact family, with increased prevalence of suicide attempt in people with high genetic risks and unfavorable environmental exposures. Conclusions: Aggregate genetic liability, childhood environmental experiences and specific socio-economic indicators are important risk factors for non-fatal suicide attempt among individuals with substance use disorder.