Genetic risk for neuroticism predicts emotional health depending on childhood adversity
AbstractBackgroundExisting evidence for gene × environment interaction (G × E) in neuroticism largely relies on candidate gene studies, although neuroticism is highly polygenic. This study aimed to investigate the long-term associations between polygenic risk scores for neuroticism (PRSN), objective childhood adversity and their interplay on emotional health aspects such as neuroticism itself, depressive symptoms, anxiety symptoms, loneliness and life satisfaction.MethodsThe sample consisted of reared-apart (TRA) and reared-together (TRT) middle- and old age twins (N= 699; median age at separation = 2). PRSNwere created under ninepvalue cut-off thresholds (pT-s) and thepTwith the highest degree of neuroticism variance explained was chosen for subsequent analyses. Linear regressions were used to assess the associations between PRSN, childhood adversity (being reared apart) and emotional health. G × E was further investigated using a discordant twin design.ResultsPRSNexplained up to 1.7% (pT< 0.01) of phenotypic neuroticism in the total sample. Analyses across two separation groups revealed substantial heterogeneity in the variance explained by PRSN; 4.3% was explained in TRT, but almost no effect was observed in TRA. Similarly, PRSNexplained 4% and 1.7% of the variance in depressive symptoms and loneliness, respectively, only in TRT. A significant G × E interaction was identified for depressive symptoms.ConclusionsBy taking advantage of a unique sample of adopted twins, we demonstrated the presence of G × E in neuroticism and emotional health using PRSNand childhood adversity. Our results may indicate that genome-wide association studies are detecting genetic main effects associated with neuroticism, but not those susceptible to early environmental influences.