Identification of Shared Genetic Variants and Haplotypes Associated With Schizophrenia and Depression

Introduction Depression is highly prevalent among individuals with schizophrenia and significantly influences disease progression, treatment response, and risk of suicide. Despite its clinical relevance, the genetic underpinnings of depression comorbidity in schizophrenia remain poorly understood. This study aimed to identify shared genetic variants and haplotypic structures contributing to the susceptibility of both conditions. Methods We systematically screened the GWAS catalog to identify genome‐wide significant variants shared between schizophrenia and depressive disorders. Linkage disequilibrium (LD) data from the 1000 Genomes Project were subsequently used to identify overlapping LD‐associated variants, followed by haplotype reconstruction using Phase 3 genotyping data. Finally, functional analyses including brain expression quantitative trait loci (eQTL) mapping and protein–protein interaction (PPI) network analysis of genes associated with the identified variants were performed to explore their potential biological relevance. Results Twelve shared GWAS variants were identified ( p < 5×10 − 6 ), among which two haplotype blocks were associated with an increased risk of both disorders, including the GTCG haplotype containing rs589249 and the GG haplotype containing rs10767735. These were integrated into a novel composite structure (GTCG–GG), which may serve as a predictive marker for the co‐occurrence of schizophrenia and depression. Additionally, rs13218591 (on BTN3A1) and rs75782365 (on BTN3A2) emerged as key shared variants (SNP p < 5×10 − 8 , PPI = 0.99). Conclusion These findings highlight potential genetic markers that may contribute to the overlapping etiology of schizophrenia and depression. The identified haplotypic structures offer promising candidates for future diagnostic panels and provide a basis for further investigating of the genetic mechanisms underlying comorbidity in psychiatric disorders.