Dysfunction of the N-methyl-D-aspartate (NMDA) receptors has been implicated in the etiology of schizophrenia based on psychotomimetic properties of several antagonists and on observation of genetic animal models. To conduct association analysis of the NMDA receptors in the Chinese population, we examined 16 reported SNPs across the NMDA receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B), five of which were identified in the Chinese population. In this study, we combined universal DNA microarray and ligase detection reaction (LDR) for the purposes of association analysis, an approach we considered to be highly specific as well as offering a potentially high throughput of SNP genotyping. The association study was performed using 253 Chinese patients with schizophrenia and 140 Chinese control subjects. No significant frequency differences were found in the analysis of the alleles but some were found in the haplotypes of the GRIN2B gene. The interactions between the GRIN1 and GRIN2B genes were evaluated using the multifactor-dimensionality reduction (MDR) method, which showed a significant genetic interaction between the G1001C in the GRIN1 gene and the T4197C and T5988C polymorphisms in the GRIN2B gene. These findings suggest that the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia.European Journal of Human Genetics (2005) 13, 807-814. doi:10.1038/sj.ejhg.5201418 Published online 20 April 2005.