Abstract
BACKGROUND: Adverse childhood experiences (ACEs) are associated with poorer mental health and may hinder educational attainment. Yet, some ACEs survivors still achieve higher education, suggesting the presence of educational resilience, whilst its underlying mechanisms remain unclear. This study aimed to evaluate the cross-cultural consistency of the ACEs-education association and to identify the underlying genetic determinants of educational resilience.
METHODS: This multi-cohort study included 127,571 UK Biobank participants, 27,128 from the Icelandic Stress-and-Gene-Analysis (SAGA) Cohort, and 4910 from the China Severe Trauma Cohort (CSTC). Associations between ACEs and educational attainment (i.e., achieving a college education or years of education) were examined using multivariable regression models. In the UK Biobank and CSTC, we performed stratification analyses by polygenic score (PGS) for educational attainment to evaluate the modifying role of genetic predisposition. We then conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with educational resilience. Resilient cases were defined as individuals exposed to ACEs in the top 10th percentile of residuals (i.e., those with the lowest 10th percentile of predicted probability of completing college who nonetheless achieved a college degree), while the remaining ACE-exposed participant served as controls. Gene-ACEs interaction analyses among all UK Biobank participants studied were used to verify the modification effects of identified variants.
FINDINGS: ACEs were associated with lower odds of obtaining a college degree across all three cohorts (odds ratio [95% confidence interval] = 0.75 [0.72-0.77] for the UK Biobank, 0.69 [0.66-0.73] for SAGA cohort, and 0.46 [0.39-0.54] for CSTC). These associations were comparable across different PGS strata both in the UK Biobank and CSTC. GWAS in the UK Biobank identified a potential novel locus (rs2743239) associated with educational resilience, mapped to several neuroprotective and immune-related pathways. We further detected a significant gene-ACEs interaction (p for interaction <0.0001) in the UK biobank, indicating that among ACEs exposed individuals, TT carriers of rs2743239 had higher odds of college completion than AA carriers (1.44 [1.21-1.71]); this trend was not observed among individuals without ACEs (1.01 [0.95-1.09]).
INTERPRETATION: ACEs were associated with lower educational attainment, irrespective of genetic predisposition to education. A potential novel variant, rs2743239, was linked to educational resilience specifically among ACEs-exposed individuals. While further validation is required, these findings offer suggestive evidence for a genetic basis of educational resilience that may inform future intervention strategies for risk management among ACEs survivors.
FUNDING: National Natural Science Foundation of China.