Haplotype association study between DRD1 gene and parasuicide in bipolar disorder: Analysis of two samples from Canada and Sardinia

Objective: Dopaminergic neurotransmission has been implicated in suicidal behaviour. Methods: In our study, three SNPs of the DRD1 gene, -800T/ C, -48A/G, and 1403T/C, were analyzed in 81 trios with at least one Bipolar patient that attempt suicide from Toronto and 31 attempters within a sample of 206 bipolar patients from Sardinia. Both the transmission disequilibrium test (TDT) and allele case-control association were performed on the genotype data to test for the presence of linkage disequilibrium between DRD1 and suicide attempt as phenotype. With the haplotype transmission disequilibrium test and haplotype case-control association (COCAPHASE), we also calculated the haplotype frequencies in Bipolar patients with and without suicide attempt. Results: Although no allele association was found in the Toronto trios and in Sardinia sample, the trend in the two samples had the same direction for all thiee SNPs, furthermore when we combined the two samples we found significant association for - 1403C (p=0.05). When we look at the haplotypes we found that the global chi-sq was not significant in both sample, however the haplotype -800C/-48G/+1403C was highly significant p--0.0006 with a Relative Risk of 5.6 in the combined sample. Conclusion: These results indicate that the -800C/-48G/ +1403C haplotype in DRD1 gene may play a role in the aetiology of parasuicide in bipolar disorder patients