The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia

Several putative schizophreniasusceptibility genes have recently been reported, but it is not clear whether these genes are associated with schizophreniain general or with specific disease subtypes. In a previous study, we found an association of the neuregulin 1(NRG1) gene with non-deficit schizophreniaonly. We now report an association study of four schizophreniacandidate genes in patients with and without deficit schizophrenia, which is characterized by severe and enduring negative symptoms. Single-nucleotide polymorphisms ( SNPs) were genotyped in the DTNBP1 ( dysbindin), G72/G30 and RGS4genes, and the relatively unknown PIP5K2A gene, which is located in a region of linkage with both schizophreniaand bipolar disorder. The sample consisted of 273 Dutch schizophreniapatients, 146 of whom were diagnosed with deficit schizophreniaand 580 controls. The strongest evidence for association was found for the A-allele of SNPrs10828317 in the PIP5K2A gene, which was associated with both clinical subtypes (P = 0.0004 in the entire group; non-deficit P = 0.016, deficit P = 0.002). Interestingly, this SNPleads to a change in protein composition. In RGS4, the G-allele of the previously reported SNP RGS4-1 (single and as part of haplotypes with SNP RGS4-18) was associated with non-deficit schizophrenia(P = 0.03) but not with deficit schizophrenia(P = 0.79). SNPsin the DTNBP1 and G72/G30 genes were not significantly associated in any group. In conclusion, our data provide further evidence that specific genes may be involved in different schizophreniasubtypes and suggest that the PIP5K2A gene deserves further study as a general susceptibility gene for schizophrenia.