Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia

Based on the dopaminergic hypothesis, the dopamine D 1 receptor gene ( DRD1 ) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (−800T/C, −48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case‐control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi‐square in both samples ( P ‐value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the −800T/−48A/1403C and the −800C/−48G/1403T. Considering each group individually, the −800C/−48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P ‐value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P ‐value = 0.16) When the estimated haplotype counts of both samples were combined, the global χ 2 was significant ( P ‐value = 0.00085) and the nominal P ‐value for the haplotype −800C/−48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the −800C/−48G/1403T haplotype may be considered as a risk factor for BP I disorder. © 2006 Wiley‐Liss, Inc.