No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population

Takenori Okumura, Tomo Okochi, Taro Kishi, Masashi Ikeda, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Kunihiro Kawashima, Tomoko Tsunoka, Hiroshi Ujike, Toshiya Inada, Norio Ozaki, Nakao Iwata

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Abstract

The neuronal nitric oxide synthase gene (NOS1) is located on 12q24, in a susceptibility region for schizophrenia, and produces nitric oxide (NO) in the brain. NO plays a role in neurotransmitter release and is the second messenger of the N-methyl-d-aspartate (NMDA) receptor. Furthermore, it is connected to the dopaminergic and serotonergic neural transmission systems. Therefore, abnormalities in the NO pathway are thought to be involved in the pathophysiology of schizophrenia. Several genetic studies showed an association of NOS1 with schizophrenia. However, results of replication studies have been inconsistent. Therefore, we conducted a replication study of NOS1 with schizophrenia in a Japanese sample. We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs2682826, and rs6490121) in NOS1 that were positively associated with schizophrenia in previous studies. Two SNPs showed an association with Japanese schizophrenic patients (542 cases and 519 controls, rs3782219: P allele = 0.0291 and rs3782206: P allele = 0.0124, P genotype = 0.0490), and almost these significances remained with an increased sample size (1154 cases and 1260 controls, rs3782219: P allele = 0.0197 and rs3782206: P allele = 0.0480). However, these associations also might have resulted from type I error on account of multiple testing (rs3782219: P allele = 0.133 and rs3782206: P allele = 0.168). In conclusion, we could not replicate the association between seven SNPs in NOS1 and schizophrenia found in several earlier studies, using larger Japanese schizophrenia and control samples.

Original languageEnglish
Pages (from-to)123-127
Number of pages5
JournalNeuroMolecular Medicine
Volume11
Issue number2
DOIs
Publication statusPublished - 01-06-2009

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Oxides
Schizophrenia
Alleles
Population
Genes
Single Nucleotide Polymorphism
Nitric Oxide
Nitric Oxide Synthase Type I
Genetic Association Studies
Second Messenger Systems
Synaptic Transmission
Sample Size
Neurotransmitter Agents
Genotype
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Okumura, Takenori ; Okochi, Tomo ; Kishi, Taro ; Ikeda, Masashi ; Kitajima, Tsuyoshi ; Yamanouchi, Yoshio ; Kinoshita, Yoko ; Kawashima, Kunihiro ; Tsunoka, Tomoko ; Ujike, Hiroshi ; Inada, Toshiya ; Ozaki, Norio ; Iwata, Nakao. / No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population. In: NeuroMolecular Medicine. 2009 ; Vol. 11, No. 2. pp. 123-127.
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abstract = "The neuronal nitric oxide synthase gene (NOS1) is located on 12q24, in a susceptibility region for schizophrenia, and produces nitric oxide (NO) in the brain. NO plays a role in neurotransmitter release and is the second messenger of the N-methyl-d-aspartate (NMDA) receptor. Furthermore, it is connected to the dopaminergic and serotonergic neural transmission systems. Therefore, abnormalities in the NO pathway are thought to be involved in the pathophysiology of schizophrenia. Several genetic studies showed an association of NOS1 with schizophrenia. However, results of replication studies have been inconsistent. Therefore, we conducted a replication study of NOS1 with schizophrenia in a Japanese sample. We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs2682826, and rs6490121) in NOS1 that were positively associated with schizophrenia in previous studies. Two SNPs showed an association with Japanese schizophrenic patients (542 cases and 519 controls, rs3782219: P allele = 0.0291 and rs3782206: P allele = 0.0124, P genotype = 0.0490), and almost these significances remained with an increased sample size (1154 cases and 1260 controls, rs3782219: P allele = 0.0197 and rs3782206: P allele = 0.0480). However, these associations also might have resulted from type I error on account of multiple testing (rs3782219: P allele = 0.133 and rs3782206: P allele = 0.168). In conclusion, we could not replicate the association between seven SNPs in NOS1 and schizophrenia found in several earlier studies, using larger Japanese schizophrenia and control samples.",
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Okumura, T, Okochi, T, Kishi, T, Ikeda, M, Kitajima, T, Yamanouchi, Y, Kinoshita, Y, Kawashima, K, Tsunoka, T, Ujike, H, Inada, T, Ozaki, N & Iwata, N 2009, 'No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population', NeuroMolecular Medicine, vol. 11, no. 2, pp. 123-127. https://doi.org/10.1007/s12017-009-8068-z

No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population. / Okumura, Takenori; Okochi, Tomo; Kishi, Taro; Ikeda, Masashi; Kitajima, Tsuyoshi; Yamanouchi, Yoshio; Kinoshita, Yoko; Kawashima, Kunihiro; Tsunoka, Tomoko; Ujike, Hiroshi; Inada, Toshiya; Ozaki, Norio; Iwata, Nakao.

In: NeuroMolecular Medicine, Vol. 11, No. 2, 01.06.2009, p. 123-127.

Research output: Contribution to journalArticle

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T1 - No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population

AU - Okumura, Takenori

AU - Okochi, Tomo

AU - Kishi, Taro

AU - Ikeda, Masashi

AU - Kitajima, Tsuyoshi

AU - Yamanouchi, Yoshio

AU - Kinoshita, Yoko

AU - Kawashima, Kunihiro

AU - Tsunoka, Tomoko

AU - Ujike, Hiroshi

AU - Inada, Toshiya

AU - Ozaki, Norio

AU - Iwata, Nakao

PY - 2009/6/1

Y1 - 2009/6/1

N2 - The neuronal nitric oxide synthase gene (NOS1) is located on 12q24, in a susceptibility region for schizophrenia, and produces nitric oxide (NO) in the brain. NO plays a role in neurotransmitter release and is the second messenger of the N-methyl-d-aspartate (NMDA) receptor. Furthermore, it is connected to the dopaminergic and serotonergic neural transmission systems. Therefore, abnormalities in the NO pathway are thought to be involved in the pathophysiology of schizophrenia. Several genetic studies showed an association of NOS1 with schizophrenia. However, results of replication studies have been inconsistent. Therefore, we conducted a replication study of NOS1 with schizophrenia in a Japanese sample. We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs2682826, and rs6490121) in NOS1 that were positively associated with schizophrenia in previous studies. Two SNPs showed an association with Japanese schizophrenic patients (542 cases and 519 controls, rs3782219: P allele = 0.0291 and rs3782206: P allele = 0.0124, P genotype = 0.0490), and almost these significances remained with an increased sample size (1154 cases and 1260 controls, rs3782219: P allele = 0.0197 and rs3782206: P allele = 0.0480). However, these associations also might have resulted from type I error on account of multiple testing (rs3782219: P allele = 0.133 and rs3782206: P allele = 0.168). In conclusion, we could not replicate the association between seven SNPs in NOS1 and schizophrenia found in several earlier studies, using larger Japanese schizophrenia and control samples.

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