title: N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses.
abstract: The N-methyl-d-aspartate glutamate receptors (NMDAR) act in the CNS as regulators of the release of neurotransmitters such as dopamine, noradrenaline, acetylcholine, and GABA. It has been suggested that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic system, which is consistent with the symptomatology of schizophrenia. We studied two silent polymorphisms in GRIN1. GRIN1/1 is a G/C substitution localized on the 5' untranslated region; GRIN1/10 is an A/G substitution localized in exon 6 of GRIN1. Minor allele frequencies in our sample were calculated to be 0.05 and 0.2 respectively. We genotyped 86 nuclear families and 91 ethnically matched case-control pairs. Both samples were collected from the Toronto area. We tested the hypothesis that GRIN1 polymorphisms were associated with schizophrenia using the transmission disequilibrium test (TDT) and comparing allele frequencies between cases and controls. The results are as follows: GRIN1/1: chi(2) = 2.19, P = 0.14; GRIN1/10: chi(2) = 1.5, P = 0.22. For the case-control sample: GRIN1/1: chi(2) = 0.013, P = 0.908; GRIN1/10: chi(2) = 0.544, P = 0.461. No significant results were obtained. Haplotype analyses showed a borderline significant result for the 2,1 haplotype (chi(2) = 3.86, P-value = 0.049). An analysis of variance (ANOVA) to evaluate the association between genetic makeup and age at onset was performed, with no significant results: GRIN1/1, F[df = 2] = 0.42, P-value = 0.659; GRIN1/10, F[df = 2] = 0.16, P-value = 0.853. We are currently collecting additional samples to increase the power of the analyses.
authors.affiliation: Neurogenetics Section, CAMH, Clarke Division, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Livia
authors.initials: L
authors.lastname: Martucci
authors.forename: Albert H C
authors.initials: AH
authors.lastname: Wong
authors.forename: Joseph
authors.initials: J
authors.lastname: Trakalo
authors.forename: Tasha
authors.initials: T
authors.lastname: Cate-Carter
authors.forename: Gregory W H
authors.initials: GW
authors.lastname: Wong
authors.forename: Fabio M
authors.initials: FM
authors.lastname: Macciardi
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution; D000704:Analysis of Variance; D002170:Canada; D016022:Case-Control Studies; D005192:Family Health; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate