Family-based association study of Synapsin II and schizophrenia

Synapsin II has been proposed as a candidate gene for vulnerability to schizophrenia on the basis of its function and its location in a region of the genome implicated by linkage studies in families with schizophrenia. We recently reported positive association of synapsin II with schizophrenia in a case-control study (Chen et al. 2004). However, since case-control analyses can generate false-positive results in the presence of minor degrees of population stratification, we have performed a replication study in 366 additional Han Chinese probands and their parents by use of analyses of transmission/disequilibrium for three in/del markers and three single-nucleotide polymorphisms. Positive association was observed for rs2307981 (P = .02), rs2308169 (P = .005), rs308963 (P = .002), rs795009 (P = .02), and rs2307973 (P = .02). For transmission of six-marker haplotypes, the global P value was .0000016 (5 degrees of freedom), principally because of overtransmission of the most common haplotype, CAA/-/G/T/C/- (frequency 53.6%; chi(2) = 20.8; P = .0000051). This confirms our previous study and provides further support for the role of synapsin II variants in susceptibility to schizophrenia.