Mutation screening has been completed for the 231-bp core promoter in195 schizophrenic individuals and 165 controls, demonstrating a complex cluster of variants (Table 3). There were12 different single-nucleotide changes, including 2 insertions and a deletion. Many of the variants lie in putative transcription factor consensus binding sequences (Figure 2B). The variant at −194 G→C introduces a new Sp1 site. In addition, we found that some subjects carried double variants that were combinations of the single variants isolated (8 different combinations). The total numbers of single and double variants found in control and schizophrenic subjects are shown in Table 3 and Table 4, respectively, stratified by ethnicity. One polymorphism, an insertion of +CGGG at −140 bp, was found in a single subject with a diagnosis of psychosis, not otherwise specified (DSM-IV, 298.9). As this diagnosis was not included in either our control or schizophrenic samples, this individual was not included in Table 3 or in the statistical analysis, but is mentioned to indicate that additional and perhaps more complex polymorphic patterns may remain to be discovered. Forty-seven of 165 control individuals and 71 of 195 schizophrenic patients had one of the single polymorphisms. Although 1 single variant (−93 bp) and 2 double variants (−93 bp/−194 bp; −191 bp/−194 bp) were found only in control subjects, a larger number of both single and double variants were found in schizophrenic patients than in controls. The difference was not, however, statistically significant. Eight of the 12 variants(−86 bp, −92 bp, −143 bp, −178 bp, −180 bp, −191 bp, −194 bp, and −241 bp), marked with asterisks in Table 3, were more prevalent in schizophrenic subjects. Twenty-seven of 165 control subjects had one of these 8 variants, but 59 were found in the 195 schizophrenic patients. Association of the single variant −86 bp C→T with schizophrenia in the combined ethnic groups reached significance (P = .04; Table 3). This polymorphism was examined alone because −86 bp C→T was the most common variant in the region, and it also had the highest prevalence in schizophrenic patients. It is found more frequently in whites than in African Americans. The genotype relative risk for this variant was 2.39 (95% confidence interval, 1.07-5.32). The principal polymorphisms found in African American schizophrenic patients were those at −178 bp del G and −191 bp G→A. Although more variants at these sites were found in schizophrenic subjects than in controls, fewer subjects were carrying each of the polymorphisms and the differences were not significant.