THE UGANDA GENOME RESOURCE–NEXUS (UGR-NEXUS): AN INTEGRATIVE MULTI-OMICS PLATFORM FOR PSYCHIATRIC GENOMICS IN AFRICA

Background African populations remain underrepresented in psychiatric genetics, limiting discovery of ancestry-specific risk variants and reducing the generalisability of psychiatric genetic findings globally. The Uganda Genome Resource–Nexus (UGR-Nexus) establishes a population-based platform integrating genomic and multi-omics data with deep psychiatric and psychosocial phenotyping to advance psychiatric genetic research in Uganda and Africa at large. Methods UGR-Nexus comprises 10,141 participants from the General Population Cohort in rural southwestern Uganda. Participants underwent detailed socio-demographic and clinical assessments, including DSM-5-aligned psychiatric evaluation for depression, generalized anxiety, suicidality, psychotic disorders, alongside characterisation of cardiometabolic traits (including gluycaemic traits, lipid traits, kidney function, blood pressure and anthropometric traits), infectious diseases (including HIV) and environmental and psychosocial exposures (including childhood trauma, life events, coping mechanisms, resilience, etc.). The platform is generating whole-genome sequencing data together with large-scale epigenetic, proteomic and metabolomic profiling, to enable integrative multi-omics analyses for psychiatric phenotypes. Results Psychiatric conditions were common, with major depressive episode identified in 16.5% of participants and major depressive disorder in 15.6%, while bipolar I disorder and any psychotic disorder were observed in 1.53% and 2.01%, respectively. Risk factors spanned socioeconomic, behavioural and psychological domains. Lower income and tobacco use were each associated with elevated odds across multiple disorders, while psychological exposures including cumulative life events and psychological distress showed the strongest and most consistent associations, with incremental increases in exposure corresponding to progressively higher disorder risk. These findings establish a deeply phenotyped foundation for the integrative genomic and multi-omics analyses of psychiatric disorders. Conclusions UGR-Nexus provides a uniquely powerful platform for psychiatric genetics in Africa, by integrating multi-omics data with deep clinical and psychiatric phenotyping within a population-based cohort in Uganda. This platform advances psychiatric genetic discovery and improves the understanding of psychiatric disorders biology in an African population.