Linkage and family-based association study of schizophrenia and the synapsin III locus that maps to chromosome 22q13

The human synapsin III gene (synapsin III) is a member of a neuron-specific phosphoprotein gene family involved in short-term neurotransmitter release . We mapped synapsin III to chromosomal region 22q13 (13.1-13.31) by fluore scence in situ hybridization, a region that has been identified as a potent ial schizophrenia susceptibility locus, The dinucleotide repeat marker D22S 280 located in intron 5 of synapsin III was genotyped in a linkage and fami ly-based association study to assess the role of the synapsin III locus in the etiology of schizophrenia. In 12 pedigrees with periodic catatonia comp rising 135 individuals, we found exclusion of linkage of marker D22S280 usi ng lod score analysis with autosomal dominant/recessive models as well as a ffected only LOD score methods with dominant/recessive models, In a family- based association study of 61 unrelated parent-offspring tries with schizop hrenia (according to the the Diagnostic and Statistical Manual of Mental Di sorders, fourth edition [DSM-IV, American Psychiatric Association, 1994]), we found no association of individual D22S280 alleles to disease. Results o f a multiallelic transmission/disequilibrium test (TDTmax = 3.00; P = 0.55) challenged the possibility that D22S280 alleles appear with DSM-IV schizop hrenia more frequently than expected, In addition, no evidence for gender d ifferences or parent-of-origin effects were found. Thus, the synapsin III l ocus at chromosome 22q13 is not likely to contain a schizophrenia susceptib ility gene. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:392-397, 2000. ( C) 2000 Wiley-Liss, Inc.