TY - JOUR
T1 - Association of SNPs linked to increased expression of SLC1A1 with schizophrenia
AU - Horiuchi, Yasue
AU - Iida, Syuhei
AU - Koga, Minori
AU - Ishiguro, Hiroki
AU - Iijima, Yoshimi
AU - Inada, Toshiya
AU - Watanabe, Yuichiro
AU - Someya, Toshiyuki
AU - Ujike, Hiroshi
AU - Iwata, Nakao
AU - Ozaki, Norio
AU - Kunugi, Hiroshi
AU - Tochigi, Mamoru
AU - Itokawa, Masanari
AU - Arai, Makoto
AU - Niizato, Kazuhiro
AU - Iritani, Shuji
AU - Kakita, Akiyoshi
AU - Takahashi, Hitoshi
AU - Nawa, Hiroyuki
AU - Arinami, Tadao
PY - 2012/1
Y1 - 2012/1
N2 - Glutamate is one of the key molecules involved in signal transduction in the brain, and dysfunction of glutamate signaling could be linked to schizophrenia. The SLC1A1 gene located at 9p24 encodes the glutamate transporter EAAT3/EAAC1. To investigate the association between the SLC1A1 gene and schizophrenia in the Japanese population, we genotyped 19 tagging single nucleotide polymorphisms (tagSNPs) in the SLC1A1 gene in 576 unrelated individuals with schizophrenia and 576 control subjects followed by replication in an independent case-control study of 1,344 individuals with schizophrenia and 1,344 control subjects. In addition, we determined the boundaries of the copy number variation (CNV) region in the first intron (Database of Genomic Variants, chr9:4516796-4520549) and directly genotyped the CNV because of significant deviation from the Hardy-Weinberg equilibrium. The CNV was not associated with schizophrenia. Four SNPs showed a possible association with schizophrenia in the screening subjects and the associations were replicated in the same direction (nominal allelic P<0.05), and, among them, an association with rs7022369 was replicated even after Bonferroni correction (allelic nominal P=5×10-5, allelic corrected P=2.5×10-4, allelic odds ratio, 1.30; 95% CI: 1.14-1.47 in the combined subjects). Expression analysis quantified by the real-time quantitative polymerase chain reaction in the postmortem prefrontal cortex of 43 Japanese individuals with schizophrenia and 11 Japanese control subjects revealed increased SLC1A1 expression levels in individuals homozygous for the rs7022369 risk allele (P=0.003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia.
AB - Glutamate is one of the key molecules involved in signal transduction in the brain, and dysfunction of glutamate signaling could be linked to schizophrenia. The SLC1A1 gene located at 9p24 encodes the glutamate transporter EAAT3/EAAC1. To investigate the association between the SLC1A1 gene and schizophrenia in the Japanese population, we genotyped 19 tagging single nucleotide polymorphisms (tagSNPs) in the SLC1A1 gene in 576 unrelated individuals with schizophrenia and 576 control subjects followed by replication in an independent case-control study of 1,344 individuals with schizophrenia and 1,344 control subjects. In addition, we determined the boundaries of the copy number variation (CNV) region in the first intron (Database of Genomic Variants, chr9:4516796-4520549) and directly genotyped the CNV because of significant deviation from the Hardy-Weinberg equilibrium. The CNV was not associated with schizophrenia. Four SNPs showed a possible association with schizophrenia in the screening subjects and the associations were replicated in the same direction (nominal allelic P<0.05), and, among them, an association with rs7022369 was replicated even after Bonferroni correction (allelic nominal P=5×10-5, allelic corrected P=2.5×10-4, allelic odds ratio, 1.30; 95% CI: 1.14-1.47 in the combined subjects). Expression analysis quantified by the real-time quantitative polymerase chain reaction in the postmortem prefrontal cortex of 43 Japanese individuals with schizophrenia and 11 Japanese control subjects revealed increased SLC1A1 expression levels in individuals homozygous for the rs7022369 risk allele (P=0.003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia.
UR - http://www.scopus.com/inward/record.url?scp=83755163055&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83755163055&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.31249
DO - 10.1002/ajmg.b.31249
M3 - Article
C2 - 22095641
AN - SCOPUS:83755163055
SN - 1552-4841
VL - 159 B
SP - 30
EP - 37
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 1
ER -