Locus-Specific Genetic Associations at the DAOA Gene in Schizophrenia and Bipolar Disorder

DAOA gene has been implicated in both schizophrenia (SZ) and bipolar disorder (BD), where genetic variants were associated with each disorder individually. However, the common variants shared between SZ and BD within this gene remain underexplored. The current study investigates locus-specific genetic variants with a focus on DAOA. A total of 120 BD and 200 SZ patients, along with equal numbers of age- and sex-matched controls from the Pakistani population, were included for genotyping, risk association analysis, haplotype, genotype-phenotype analysis, and clinical correlations. The DAOA SNP rs2391191 (G/A) showed a nominal association with both SZ and BD. In contrast, rs1935062 showed no association with either disorder, but genotype-phenotype analysis indicated nominal associations with disorder-specific clinical features, such as insomnia and disorganized thoughts in BD, and restricted mood and feelings of threat in SZ patients. Our findings suggest locus-specific associations for SZ and BD at the DAOA locus; however, due to the limited sample size, these findings should be considered exploratory and require further validation in larger cohorts. Further, patterns of allele frequencies and effect sizes diverge from several European studies and global reports, highlighting the population-specific genetic architecture and allelic heterogeneity.