BACKGROUND: N-methyl-D-aspartate (NMDA) receptors play important roles in many neurophysiological processes. Evidence from previous studies indicate that NMDA receptors contribute to the pathophysiology of schizophrenia. Two NMDA receptor subunit genes, GRIN1 and GRIN2A, are both good candidate genes for schizophrenia. METHOD: We genotyped five single nucleotide polymorphisms (SNPs) in GRIN1 and two in GRIN2A in 2455 Han Chinese subjects, including population- and family-based samples, and performed case-control and transmission disequilibrium test (TDT) analyses. A microsatellite in GRIN2A was genotyped in population-based samples and a Mann-Whitney U test was performed. RESULTS: A highly significant association was detected at the 5' end of GRIN1. Analyses of single variants and multiple-locus haplotypes indicate that the association is mainly generated by rs11146020 (case-control study: p = .0000013, odds ratio = .61, 95% confidence interval .50-.74; TDT: p = .0019, T/NT = 79/123). No association was found in the GRIN2A polymorphisms. CONCLUSIONS: Our results provide support for the hypothesis that NMDA receptors are an important factor in schizophrenia. Moreover, rs11146020 is located in 5' untranslated region where several functional elements have been found. Hence, the SNP is a potential candidate in altering risk for schizophrenia and worthy of further replication and functional study.
BACKGROUND: N-methyl-D-aspartate (NMDA) receptors play important roles in many neurophysiological processes. Evidence from previous studies indicate that NMDA receptors contribute to the pathophysiology of schizophrenia. Two NMDA receptor subunit genes, GRIN1 and GRIN2A, are both good candidate genes for schizophrenia. METHOD: We genotyped five single nucleotide polymorphisms (SNPs) in GRIN1 and two in GRIN2A in 2455 Han Chinese subjects, including population- and family-based samples, and performed case-control and transmission disequilibrium test (TDT) analyses. A microsatellite in GRIN2A was genotyped in population-based samples and a Mann-Whitney U test was performed. RESULTS: A highly significant association was detected at the 5' end of GRIN1. Analyses of single variants and multiple-locus haplotypes indicate that the association is mainly generated by rs11146020 (case-control study: p = .0000013, odds ratio = .61, 95% confidence interval .50-.74; TDT: p = .0019, T/NT = 79/123). No association was found in the GRIN2A polymorphisms. CONCLUSIONS: Our results provide support for the hypothesis that NMDA receptors are an important factor in schizophrenia. Moreover, rs11146020 is located in 5' untranslated region where several functional elements have been found. Hence, the SNP is a potential candidate in altering risk for schizophrenia and worthy of further replication and functional study.
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Sarah S Murray; Kristin S Cadenhead; Monica E Calkins; Dorcas J Dobie; Michael F Green; Raquel E Gur; Ruben C Gur; Gary Hardiman; John R Kelsoe; Sherry Leonard; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Robert Freedman; David L Braff Journal: Am J Psychiatry Date: 2011-04-15 Impact factor: 18.112
Authors: M J Gandal; J Sisti; K Klook; P I Ortinski; V Leitman; Y Liang; T Thieu; R Anderson; R C Pierce; G Jonak; R E Gur; G Carlson; S J Siegel Journal: Transl Psychiatry Date: 2012-07-17 Impact factor: 6.222
Authors: Irina Voineagu; Xinchen Wang; Patrick Johnston; Jennifer K Lowe; Yuan Tian; Steve Horvath; Jonathan Mill; Rita M Cantor; Benjamin J Blencowe; Daniel H Geschwind Journal: Nature Date: 2011-05-25 Impact factor: 49.962