Study Report

Reference	Muir, W. J.,2001 PMID: 11304828
Citation	Muir, W. J., M. L. Thomson, et al. (2001). "Markers close to the dopamine D5 receptor gene (DRD5) show significant association with schizophrenia but not bipolar disorder." Am J Med Genet 105(2): 152-158.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	158 schizophrenic subjects,270 patients with bipolar disorder,65 subjects with recurrent unipolar disorder and 437 controls
SNP/Region/Marker Size	1 variant
Predominant Ethnicity	Caucasian
Population	Scottish

Sample Diagnosis	DSM
Sample Status	Case/Control Comparisons:Inpatients and outpatients of Southeast Scotland and Ireland psychiatric services were invited to participate after giving informed consent. DSM-IV [American Psychiatric Association, 1994] diagnoses of definite schizophrenia, bipolar disorder, or recurrent unipolar disorder were reached after interview by a psychiatrist using SADS-L [Endicott and Spitzer, 1978] and a case note review. All 158 schizophrenic subjects were resident in Southeast Scotland. Of the total group of 270 patients with bipolar disorder, 184 were from Southeast Scotland and 86 were from Ireland. All 65 subjects with recurrent unipolar disorder were from Southeast Scotland. The 437 controls without psychiatric illness comprised 292 from Southeast Scotland, 87 blood donors from Ireland, and 58 members of CEPH pedigrees. Linkage Analysis:DNA samples from 12 Scottish families multiply affected with schizophrenia were genotyped. Details of these families have been published previously [St Clair et al., 1989].
Technique	PCR and electrophoresis
Statistical Method	Case-control allele frequency comparisons used the CLUMP [Sham and Curtis, 1995] and EH [Xie and Ott,1993; Zhao et al., 2000] programs.To test for linkage given association, the transmission test for linkage disequilibrium(TDT) [Spielman and Ewens, 1996] was applied to a series of affected offspring and parents trios where the offspring had schizophrenia and where at least one parent was heterozygous for a given marker.
Result Summary	A significant increase in the frequency of the 148 bp allele of DRD5 (P = 0.024) and the 244 bp allele of D4S615 (P = 0.001) was found in patients with schizophrenia (n = 158 DRD5; n = 133 D4S615), compared with patients with bipolar disorder (n = 270 DRD5; n = 107 D4S615), or controls without psychiatric illness (n = 437 DRD5; n = 309 D4S615). The frequency of the 148 bp allele of DRD5 was also increased in schizophrenia over unipolar major depressive disorder (n = 65). D4S615 was not typed in unipolar disorder. The estimated odds ratios confirmed that the 148 bp allele of DRD5 and the 244 bp allele of D4S615 conferred increased risk of schizophrenia. Estimated Haplotype (EH) analysis of 174 controls and 128 patients with schizophrenia who were typed for both markers confirmed the strong associations with these alleles but did not show evidence that the markers were in linkage disequilibrium with each other even though they lie approximately 150 kb apart. The data are consistent with an association between markers close to the D5 dopamine receptor and schizophrenia, but not bipolar disorder or unipolar major depression.