COMMON COMPONENT AND PSYCHIATRIC DISORDER SPECIFIC POLYGENIC RISK SCORE EFFECTS ON EMOTIONAL AND BEHAVIOURAL TRAJECTORIES IN YOUNG PEOPLE

Background Emotional and behavioral dysregulation is commonly present in severe mental illnesses, including schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD). These disorders exhibit highly polygenic architectures with substantial genetic overlap. While polygenic risk scores (PRS) for these disorders have been linked to general psychopathology, the distinct contributions of shared versus disorder-specific genetic components on developmental trajectories remain unclear. This study explores how PRS—decomposed via genomic structural equation modelling (gSEM)[1] into shared and disorder-specific genetic factors—shape emotional and behavioural symptom trajectories in youth. Methods Using longitudinal data from the UK Millennium Cohort Study[2], we applied group-based trajectory modelling to parent-reported Strengths and Difficulties Questionnaire (SDQ) scores (ages 3–17). The SDQ questionnaires included eight domains: five core SDQ subscales (emotional symptoms, conduct problems, hyperactivity/inattention, peer problems, prosocial behaviour) and three composites (internalizing, externalizing, total difficulties)[3]. PRSs were derived from gSEM components: a shared factor (PRS-Shared) and disorder-differentiating scores for SCZ (PRS-SCZ-Diff), BIP (PRS-BD-Diff), and MDD (PRS-MDD-Diff) using PRSice2 [4]. Associations between PRSs and trajectory classes were tested via multinomial logistic regression, adjusting for sex, age, and the first 10 genetic principal components. Sensitivity analyses employed PRS-cs-auto [5] to validate the results. Results A total of 6,300 children (49.7% girls) were included in the analysis. Group-based trajectory modelling identified 3 distinct trajectory classes in total difficulties, internalizing problems, prosociality, peer problems, and conduct problems; 4 classes in emotional symptoms; and 5 classes in externalizing problems and hyperactivity. PRS-Shared was positively associated with persistent difficulties in conduct (class 2: RR, 1.13; 95% CI, 1.05–1.22; P = 0.002; class 4: RR, 1.11; 95% CI, 1.02–1.22; P = 0.02), emotional symptoms (class 2: RR, 1.06; 95% CI, 1.01–1.12; P = 0.03; class 3: RR, 1.14; 95% CI, 1.05–1.25; P = 2.0 × 10⁻³), internalizing (class 2: RR, 1.07; 95% CI, 1.01–1.12; P = 0.017; class 3: RR, 1.10; 95% CI, 1.01–1.20; P = 0.034), and externalizing (class 2: RR, 1.11; 95% CI, 1.00–1.22; P = 0.043) domains. PRS-MDD-Diff was positively associated with all seven trajectory domains (P < 0.05) except prosociality. PRS-BD-Diff showed negative associations with hyperactivity (class 5: RR, 0.89; 95% CI, 0.80–1.00; P = 0.046), peer problems (class 2: RR, 0.92; 95% CI, 0.88–0.97; P = 2.6 × 10⁻³; class 3: RR, 0.91; 95% CI, 0.83–1.00; P = 0.04), and internalizing trajectories (class 2: RR, 0.89; 95% CI, 0.81–0.97; P = 7.6 × 10⁻³; class 3: RR, 0.94; 95% CI, 0.90–0.99; P = 0.029). PRS-SCZ-Diff was not associated with any psychopathological trajectory classes. Sensitivity analyses confirmed these trends. Discussion This study integrates gSEM-derived PRSs with longitudinal developmental trajectories in youth, showing that shared genetic liability predicts persistent emotional and behavioral difficulties as a transdiagnostic risk factor. PRS-MDD-Diff emerges as a broad early marker across symptom domains, highlighting the value of genetically informed trajectory analyses for understanding heterogeneous mental health pathways.