Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region.
The glutamatergic dysfunction hypothesis suggests that genes involved in the glutamate neurotransmitter system are candidates for schizophrenia-susceptibility genes. We have been conducting systematic studies of the association between glutamate receptors and schizophrenia. We report on a positive association of some haplotypes of the AMPA receptor subunit GluR4 gene (GRIA4) with schizophrenia. We genotyped 100 Japanese schizophrenics and 100 controls for six single nucleotide polymorphism (SNP) markers distributed at intervals of about 50 kb in the GRIA4 region, and estimated the degree of linkage disequilibrium (LD) between the SNPs. We constructed haplotypes of the SNPs in LD using the EM algorithm to test their association with schizophrenia. Significant associations were detected for the combination of SNP4-5 (chi(2) = 12.54, df = 3, P = 0.0057, P = 0.029 with Bonferroni correction) and for the combination of SNP3-4-5 (chi(2) = 18.9, df = 7, P = 0.0085, P = 0.043 with Bonferroni correction). These results suggest that at least one susceptibility locus for schizophrenia is located within or very close to the GRIA4 region in Japanese.
Makino
Chieko
C
Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Fujii
Yo
Y
Kikuta
Rumiko
R
Hirata
Naotsugu
N
Tani
Ayako
A
Shibata
Atsushi
A
Ninomiya
Hideaki
H
Tashiro
Nobutada
N
Shibata
Hiroki
H
Fukumaki
Yasuyuki
Y
D000483:Alleles; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D004247:DNA