Association of synapsin 2 with schizophrenia in families of Northern European ancestry

Abstract

The synapsin 2 (Syn2) gene (3p25) is implicated in synaptogenesis, neurotransmitter release, and the localization of nitric oxide synthase to the proximity of its targets. In this study we investigated linkage and association between the Syn2 locus and schizophrenia. 37 pedigrees of Northern European ancestry from the NIMH Human Genetics Initiative collection were used. Four microsatellites and twenty SNPs were genotyped. Linkage (FASTLINK) and association (TRANSMIT, PDTPHASE) between markers and schizophrenia were evaluated. A maximum heterogeneity LOD of 1.93 was observed at marker D3S3434 with a recessive mode of inheritance. Significant results were obtained for association with schizophrenia using TRANSMIT (minimum nominal p=0.0000005) and PDTPHASE (minimum nominal p=0.014) using single marker analyses. Haplotype analysis using markers in introns 5 and 6 of Syn2 provided a single haplotype that is significantly associated with schizophrenia using TRANSMIT (nominal p<0.00000001) and PDTPHASE (nominal p=0.02). Simulation studies confirm the global significance of these results, but demonstrate that the small p-values generated by the bootstrap routine of TRANSMIT can be consistently anticonservative. Review of the literature suggests that Syn2 is likely to be involved in the etiology or pathogenesis of schizophrenia.

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

“…While neither RASD1, DYNLL1 (which have not yet been specifically tested before) nor SYN2 (which had some prior evidence; (Saviouk et al, 2007)) gave a significant signal, SNPs in NOS1AP and NOS1 did; both genes in the present case-control studies and the latter also in the meta-analysis. These SNPs have been previously suggested to contribute to schizophrenia liability, and most interestingly, they also interacted in increasing disease risk.…”

Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity

“…CAMk1D is a Ca 2+ /calmodulin dependent kinase predominantly expressed in polymorphonuclear cells, among hematopoietic cell lines (Verploegen et al, 2000). In in vitro assays, CAMk1D phosphorylated several substrates, including synapsin 1 and 2, and CREB (Nairn and Greengard, 1987;Sheng et al, 1991), which were previously associated with SCZ (Fei et al, 2010;Kawanishi et al, 1999;Saviouk et al, 2007). The binding of Ca 2+ to calmodulin is a signal transducing mechanism of Ca 2+ into cellular responses that regulate many crucial processes (Chin and Means, 2000).…”

Genome‐wide scan in 124 Indonesian sib‐pair families with schizophrenia reveals genome‐wide significant linkage to a locus on chromosome 3p26‐21

“…The gene is located at the distal end of the peak at 0.2 Mb, whilst the gene SYN2 (synapsin II) is located at the proximal site of the linkage peak. SYN2 has been reported to be associated with schizophrenia in several studies [Chen et al, 2004a,b;Lee et al, 2005;Saviouk et al, 2007].…”