Background: Schizophrenia and bipolar disorder are common and often destructive brain disorders. It has generally been assumed that dozens of genes, along with environmental factors, contribute to the development of these diseases. Schizophrenia and bipolar mood disorder affect many families simultaneously. This theme suggests that these disorders have a shared genetic etiology at least to some extent. The DAOA/G72 gene is one of the common loci shared both by schizophrenia and bipolar disorder. The functions of this gene could converge in a pathway of glutamate metabolism. Objectives: The purpose of the study was determination of genetic overlap between affective disorders using association analysis of M18 and M23 SNPs of DAOA/G72 gene with schizophrenia and bipolar disorder. Patients and Methods:In this case-control study, in order to evaluate the potential association of DAOA gene with schizophrenia and bipolar disorder in a southwest Iran population, two single nucleotide polymorphisms M18 and M23 were genotyped by the PCR-RFLP method and sequencing assay in 127 normal controls and 100 patients with schizophrenia and 100 patients with bipolar disorder. Data were analyzed by Logistic Regression and Mantel-Haenszel chi square tests. Results: Our finding showed that the M18 was significantly associated with bipolar disorder. We observed there is overlap association in M23 with schizophrenia and bipolar disorder. Also, our results indicated that the coexistence of the A and T alleles from the two polymorphisms, M18 and M23, increase the risk for schizophrenia and bipolar disorder. Conclusions: In summary, our data provides further evidence for a positive association between the DAOA locus and schizophrenia and bipolar disorder, these results may provide further support for genetic overlap in DAOA gene between schizophrenia and bipolar disorder.