Investigating the contribution of childhood maltreatment to suicide attempt: A multivariable Mendelian randomization study

• Childhood maltreatment has been associated with suicide attempt. • Few quasi-experimental studies have accounted for the confounding factors. • Mendelian randomization was used to account for confounding factors. • Maltreatment contributed to a 4-fold increase in suicide attempt risk. • This was mostly explained by mental disorders, socioeconomic, and cognitive factors. Childhood maltreatment has been associated with suicidal behavior. However, whether this risk is causal and uniquely due to consequences of childhood maltreatment such as mental disorders, socioeconomic difficulties, and cognitive skills impairments needs clarification. We investigated direct and indirect contributions of childhood maltreatment to suicide attempt using a two-sample multivariable Mendelian randomization design. We used 7 single nucleotide polymorphisms from the childhood maltreatment genome-wide association study as instruments for childhood maltreatment. Multivariable Mendelian randomization was used to investigate the association of childhood maltreatment with suicide attempt accounting for risk of major psychiatric disorders (major depression, schizophrenia, attention-deficit/hyperactivity disorder), cognitive factors, and socioeconomic factors. Evidence supported a possible causal role of childhood maltreatment on suicide attempt (OR 4.36, CI 2.36-7.97). Significant associations with suicide attempt were identified for subtypes of maltreatment (physical abuse, physical neglect, emotional abuse, emotional neglect, sexual abuse), although unclear for sexual abuse. In multivariable analyses, childhood maltreatment was associated with suicidal attempt independently from selected mental disorders, socioeconomic factors, and cognitive factors although these factors accounted for most of the association (OR 1.51, CI 1.10-2.09). To prevent suicide among children exposed to maltreatment, it may be important to combine interventions to reduce mental disorders, psychosocial intervention, and suicide-specific preventive intervention.