EVIDENCE FOR AN ASSOCIATION BETWEEN THE DOPAMINE D3 RECEPTOR GENE DRD3 AND SCHIZOPHRENIA

Association of the dopamine D3 receptor gene (DRD3) and schizophrenia was examined in unrelated Israeli and Italian schizophrenic patients a nd ethnically matched normal control subjects. In the combined sample, there was a siginificant excess of DRD3 allele 2 among the schizophre nic patients (chi(2) = 4.70, d.f. I, p = 0.03). Comparison of genotype frequencies revealed an excess of the 2-2 genotype in the combined sc hizophrenic sample (chi(2) = 8.30, d.f. 1, p = 0.01) and in the non-As hkenazi Israeli schizophrenics alone (chi(2) = 5.70, d.f. 2, p = 0.05) . DRD3 2-2 genotype conferred a significantly increased risk of schizo phrenia (chi(2) = 8.21, d.f. 1, p = 0.004; OR = 2.87, CI 95% = 1.36-5. 76) in the combined sample and in the non-Ashkenazi Israeli schizophre nics (chi(2) = 7.22, d.f. 1, p = 0.04; OR = 7.22, CI 95% = 1.04-24.83) . In the combined and Italian samples, allele 2 was associated with ea rly age of onset as was the 2-2 genotype in the combined sample and no n-Ashkenazi group. The 2-2 genotype was associated with poor response to neuroleptics, particularly in the non-Ashkenazi, Israeli schizophre nics. The possibility that DRD3 or a locus in linkage disequilibrium w ith it may play a role in the transmission of schizophrenia, is consid ered in relation to previous positive and negative reports.