Serotonergic multilocus genetic variation moderates the association between major interpersonal stress and adolescent depressive symptoms: Replication and candidate environment specification

Abstract Serotonin-linked genetic risk and stressful life event (SLE) interaction research has been criticized for using single genetic variants with inconsistent replicability. A recent study showed that a multilocus genetic profile score (MGPS) capturing additive risk from five serotonin-linked polymorphisms moderated the association between major interpersonal SLEs and depression, but no subsequent replication attempts have been reported. Moreover, major interpersonal SLEs have been suggested as “candidate environments” for this MGPS, but it has never been demonstrated that gene-environment interactions (G × Es) for major interpersonal SLEs are significantly stronger than for other contexts. Adolescents ( N  = 241) completed contextual-threat life stress interviews and clinical interviews assessing depressive symptoms, and provided DNA. MGPS intensified the major interpersonal stress-depression association; the interaction accounted for 4% of depressive symptom variance. Genetic moderation was statistically unique to major interpersonal stress versus other environments. Extending previous findings, results support an MGPS approach and underscore the cruciality of the G × E candidate environment.