Bipolar Disorder type 1 (BP-1) is a severe and common psychiatric disorder with a strong genetic contribution to increased disease risk. Heritability is around 60% and at least a dozen different genes seems to be involved in the etiology. The DAOA-G72/G30) locus on chromosome 13p22-34 has been associated with BP-1 in at least six independent datasets, although there are different SNPs and haplotypes associated with increased disease risk in these studies.

276 Swedish patients with BP-1, diagnosed according to DSM-IV, and 940 controls were analyzed with 36 SNPs from eight previously reported candidate genes for bipolar disorder (DAOA-G72/G30, P2RX7, COMT, BDNF, CAMKK2, GRK3, SLC6A4 and S100A10). Genotyping was carried out with Applied Biosystems TaqMan® using ABI PRISM® 7900HT Sequence Detecting System. Statistical analysis was performed with the Unphased program.

None of the SNPs showed a significant association by itself. However, three SNPs in different haplotype blocks in the DAOA-G72/G30 genes were together associated to bipolar disorder (p=0.0009). The association remained when different SNPs in each haplotype block were analyzed.

This is the first study of the G72/30 gene in a homogeneous Swedish BP-1 sample. We found a strong association, which required SNPs from three different haplotype blocks. Thus, the association between the DAOA-G72/G30 genes and Swedish patients with BP-1 disorder was more complex than previous findings.