Interest in the molecular basis of the P50 phenotype was spurred by a 1997 report that a locus on chromosome 15 had been identified by linkage mapping (Freedman et al. 1997). The report was important because the locus contained a gene, the alpha 7-nicotinic acid receptor, which was later reported by the same group to be significantly associated with failure to inhibit the P50 auditory-evoked potential (Leonard et al. 2002). Furthermore, the group has presented evidence that functional variants in the promoter of the gene are present at significantly greater frequencies in schizophrenia subjects compared to controls (Leonard et al. 2002). A second group has independently reported that a 2 bp deletion in exon 6 of the gene and a polymorphism in the promoter are associated with the P50 phenotype (Raux et al. 2002; Houy et al. 2004) but not with schizophrenia. Clearly, given the findings for other complex traits, these results must be replicated in large samples if they are to be regarded as genuine.
