Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1)

Schizophrenia is a common, genetically heterogeneous disorder with a lifeti me prevalence of approximately 1% in the general population. Linkage studie s of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN's) or s usceptibility mutations to within a few hundred kilobases. Three brain expr essed candidate susceptibility genes, prepronociceptin (PNOC), neuronal cho linergic receptor, nicotinic, alpha polypeptide 2 (CHRNA2) and arylamine N- acetyltransferase 1 (NAT1) have been mapped to chromosome 8p21-22. A case-c ontrol, allelic association study was performed using a novel highly polymo rphic dinucleotide repeat, D8S2611 near the PNOC gene, two previously chara cterised dinucleotide repeats, D8S131 and D8S131P at the CHRNA2 locus and a n RFLP at the 3 ' UTR of the arylamine N-acetyltransferase 1 (NAT1) gene. N o differences were found in allele frequencies between the patient and cont rol groups. DNA variations or mutations at or near the three genes under st udy are unlikely to increase susceptibility to schizophrenia in our populat ion sample.