In 141,087 UKB-non-NI participants, we identified urban environmental profiles correlated to psychiatric symptom groups using sCCA with a train–test dataset split design. Next, we carried out GWAS analyses of the symptom groups in 76,508 participants with complete genomic, urban environmental categories and psychiatric symptoms from the UKB-non-NI dataset. The UKB-NI dataset data ( n = 14,988) was used for independent replication of the multivariate relationship between urban environmental profiles, genes and symptom groups, and for additional neuroimaging analyses. We analyzed the relationships between urban environmental profiles, regional brain volume and symptom groups using msCCA with a train–test dataset split design. Using a moderated mediation analysis, we then investigated the interaction effect between urban environmental profiles and genetics on psychiatric symptoms groups mediated by brain components in 8,705 participants with complete genomic, urban environmental categories, regional brain volume and symptoms of mental illness in the UKB-NI dataset.