Childhood maltreatment moderates associations between SKA2 DNA methylation and suicidal ideation in african american adults with bipolar disorder.

Individuals with Bipolar Disorder experience disproportionately high rates of suicidal ideation and behavior, however, findings regarding biologically informed biomarkers of suicide risk have been inconsistent and have largely been studied without consideration to environmental context or potential population-level differences. Epigenetic mechanisms, such as DNA methylation, may capture genetic-environmental interactions relevant to suicide risk. The present study examined associations between suicidal ideation and DNA methylation of the spindle and kinetochore-associated protein 2 (SKA2) gene, a stress-related gene involved in the hypothalamic-pituitary-adrenal axis regulation. We also tested childhood maltreatment as a moderator of these associations. Participants included 127 under-resourced African American adults with Bipolar Disorder. No direct associations between SKA2 methylation and suicidal ideation were observed. However, childhood maltreatment significantly moderated the association between SKA2 methylation and suicidal ideation, specifically within the intronic region of the gene. Lower intronic SKA2 methylation was associated with greater levels of suicidal ideation among individuals exposed to extremely severe levels of childhood maltreatment. Sensitivity analyses revealed that this pattern was specific to emotional abuse and physical neglect. These findings suggest that intronic SKA2 methylation may represent a context-dependent correlate of suicidal ideation, with associations primarily observed among individuals reporting substantial early-life adversity. Results underscore the importance of considering developmental trauma history when evaluating epigenetic correlates of suicide risk in under-resourced, historically underrepresented populations.