Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia.
Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population.
Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, and Fukuoka Prefectural Dazaifu Hospital Psychiatric Center, Fukuoka, Japan. hshibata@gen.kyushu-u.ac.jp
Hiroki
H
Shibata
Ayako
A
Tani
Tomoyuki
T
Chikuhara
Rumiko
R
Kikuta
Mayumi
M
Sakai
Hideaki
H
Ninomiya
Nobutada
N
Tashiro
Nakao
N
Iwata
Norio
N
Ozaki
Yasuyuki
Y
Fukumaki
D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017470:Receptors, Glutamate / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate