Several putative
schizophrenia susceptibility genes have recently been reported, but it is not clear whether these genes are associated with
schizophrenia in general or with specific disease subtypes. In a previous study, we found an association of the
neuregulin 1 (NRG1) gene with non-deficit
schizophrenia only. We now report an association study of four
schizophrenia candidate 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 RGS4 genes, and the relatively unknown PIP5K2A gene, which is located in a region of linkage with both
schizophrenia and
bipolar disorder. The sample consisted of 273 Dutch
schizophrenia patients, 146 of whom were diagnosed with deficit
schizophrenia and 580 controls. The strongest evidence for association was found for the A-allele of SNP rs10828317 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 SNP leads 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). SNPs in 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
schizophrenia subtypes and suggest that the PIP5K2A gene deserves further study as a general susceptibility gene for
schizophrenia.