title: Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia.
abstract: We have reported an association between schizophrenia and homozygosity of a Bal I polymorphism in the first exon of the dopamine D3 receptor gene (Crocq et al.: Journal of Medical Genetics 29:858-860, 1992). The present study consists of an attempt to replicate this finding in a further sample of 66 patients and 97 controls. Once again more patients than controls were homozygous, but the effect was not as strong as in our first study (chi 2 = 2.53, P = 0.05, one tailed). When pooled data from our two studies were analysed, excess homozygosity in patients remained highly significant (P = 0.002) with a particular excess of the 1:1 genotype (P = 0.01). This reflected a departure from Hardy-Weinberg equilibrium in the patients (P = 0.0005) but not the controls (P = 0.24). This led us to explore the possibility that there might be important differences between the patients in our two studies and that excess homozygosity might be a characteristic of particular subgroups of schizophrenics. Our findings suggest that the effect is consistently at its strongest in those patients who have a high familial loading and in those who have a good response to neuroleptic treatment, and that differences between our two samples might have contributed to the quantitatively different outcomes.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Mant
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Asherson
authors.forename: E
authors.initials: E
authors.lastname: Parfitt
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D017931:DNA Primers; C493593:DRD3 protein, human; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015252:Deoxyribonucleases, Type II Site-Specific; C060616:TGGCCA-specific type II deoxyribonucleases