Giulia Trotta, Isabelle Austin-Zimmerman, Edoardo Spinazzola, Senta M. Haussler, Lucia Sideli, Monica Aas, Victoria Rodríguez, Zhikun Li, Perry BM Leung, Qiang Li, D. Quattrone, Craig Morgan, Michael O’Donovan, P Sham, Evangelos Vassos, Chloe CY Wong, Richard P. Bentall, Robin Murray, Luis Alameda, Marta Di Forti
BACKGROUND: Childhood trauma is a well-known environmental risk factor for psychiatric disorders, yet genetic influences may also shape exposure to adversity via gene-environment correlation (rGE). METHODS: We examined rGE between polygenic risk scores (PRSs) for psychiatric and behavioral traits and trauma subtypes across development in 2 large cohorts: the EU-GEI (European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) case-control study (n = 1191) and the ALSPAC (Avon Longitudinal Study of Parents and Children) birth cohort (N = 8141). Trauma was assessed retrospectively in EU-GEI and both prospectively and retrospectively in ALSPAC. Multinomial logistic regressions tested associations between PRSs and timing of exposure (early: 0-11 years vs. late: 12-17 years) to 5 trauma types (emotional abuse, physical abuse, sexual abuse, bullying, and household discord). RESULTS: In EU-GEI, 20 PRS-trauma associations survived false discovery rate correction. The posttraumatic stress disorder PRS showed strong associations with early emotional abuse (odds ratio [OR] = 3.37), sexual abuse (OR = 3.08), physical abuse (OR = 2.90), and bullying (OR = 2.19). Attention-deficit/hyperactivity disorder (ADHD) PRS was linked to early sexual abuse (OR = 1.49), emotional abuse (OR = 1.33), household discord (OR = 1.27), and bullying (OR = 1.24). Schizophrenia (SCZ) PRS was associated with early emotional abuse (OR = 1.90) and late bullying (OR = 1.46). In ALSPAC, 20 PRS-trauma associations were replicated, including ADHD, depression, bipolar disorder, SCZ, and cannabis use disorder with early traumas. Variance explained was small in both cohorts. Sensitivity analyses restricted to control participants in EU-GEI confirmed results. CONCLUSIONS: These findings provide novel and robust evidence for rGE between psychiatric PRSs and specific trauma exposures, particularly in early development, underscoring the importance of incorporating genetic liability in trauma research.