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UHMK1 has previously been implicated as a susceptibility gene for schizophrenia in the 1q23.3 region by significant evidence of allelic and haplotypic association between schizophrenia and several genetic markers at UHMK1 in a London-based case–control sample. Further fine mapping of the UHMK1 gene locus in the University College London schizophrenia case–control sample was carried out with tagging SNPs. Two additional SNPs were found to be associated with schizophrenia (rs6604863 P=0.02, rs10753578 P=0.017). Tests of allelic and haplotypic association were then carried out in a second independent sample from Aberdeen consisting of 858 individuals with schizophrenia and 591 controls. Two of these SNPs also showed association in the Aberdeen sample (rs7513662 P=0.0087, rs10753578 P=0.022) and several haplotypes were associated (global permutation P=0.0004). When the UCL and Aberdeen samples were combined three SNPs (rs7513662 P=0.0007, rs6427680 P=0.0252, rs6694863 P=0.015) and several haplotypes showed association (eg HAP-A, HAP-B, HAP-C permutation P=0.00005). The finding of allelic association with markers in the UHMK1 gene might help explain why it has not been possible, despite great effort, to satisfactorily confirm previously reported associations between schizophrenia and the genes RGS4 and NOS1AP/CAPON. These genes flank UHMK1 and all three loci are within a 700 kb region showing linkage to schizophrenia. The confirmation of association between UHMK1 and schizophrenia, rather than RGS4 and NOS1AP in the London sample, points to the possibility that previous efforts to accurately fine map a gene in the 1q23.3 region have lacked accuracy or may have suffered from methodological flaws.European Journal of Human Genetics (2008) 16, 1275–1282; doi:10.1038/ejhg.2008.76; published online 16 April 2008 [ABSTRACT FROM AUTHOR]

Background: Previous linkage and association studies may have implicated the Dystrobrevinbinding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. Methods: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. Results: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. Conclusion: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family. [ABSTRACT FROM AUTHOR]

Background: Linkage studies have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. It was then claimed that markers at the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) gene showed allelic association with schizophrenia in Canadian families. A second Chinese study found a base pair polymorphism at the CAPON gene also associated with schizophrenia. Methods: We attempted replication using eight markers from the Canadian study in a UK based sample of 450 cases and 450 supernormal controls. Results: We found no evidence for allelic or haplotypic association with schizophrenia for any of the markers found to be associated in the Canadian sample. Conclusions: The negative results might reflect genetic heterogeneity between the Canadian, Chinese and UK samples or be due to methodological problems. The present finding weakens the evidence that mutations or variation in the CAPON gene are causing genetic susceptibility to schizophrenia in European populations. [Copyright &y& Elsevier]