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Genetic association analysis of tagging SNPs in alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes (CHRNA4 and CHRNB2) with schizophrenia in the Japanese population

  • Biological Psychiatry - Original Article
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Abstract

Several lines of evidence suggest that nicotinic cholinergic dysfunction may contribute to the cognitive impairments in schizophrenia. The majority of high affinity nicotine binding sites in the human brain have been implicated in heteropentameric alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptors; therefore, these two neuronal nicotinic acetylcholine receptors genes (CHRNA4 and CHRNB2) are considered to be attractive candidate genes for the pathophysiology of schizophrenia. To represent these two genes in a gene-wide manner, we first evaluated the linkage disequilibrium structure using our own control samples. Thirteen SNPs (7 SNPs for CHRNA4 and 5 SNPs for CHRNB2) were selected as tagging SNPs. Using these tagging SNPs, we then conducted genetic association analysis of case-control samples (738 schizophrenia and 753 controls) in the Japanese population. No significant association was detected in the allele/genotype-wise or haplotype-wise analysis. Our results suggest that CHRNA4 and CHRNB2 do not play a major role in Japanese schizophrenia.

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Acknowledgments

We thank Ms M. Miyata and Ms S. Nakaguchi for their technical support. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare, and the Japan Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation).

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Authors and Affiliations

  1. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan

    Taro Kishi, Masashi Ikeda, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Kunihiro Kawashima, Tomo Okochi & Nakao Iwata

  2. Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Norio Ozaki

  3. Neuropsychiatric Research Institute, Seiwa Hospital, Tokyo, Japan

    Toshiya Inada

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  1. Taro Kishi
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  2. Masashi Ikeda
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  3. Tsuyoshi Kitajima
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  4. Yoshio Yamanouchi
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  5. Yoko Kinoshita
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  6. Kunihiro Kawashima
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  9. Norio Ozaki
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  10. Nakao Iwata
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Correspondence to Taro Kishi.

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Kishi, T., Ikeda, M., Kitajima, T. et al. Genetic association analysis of tagging SNPs in alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes (CHRNA4 and CHRNB2) with schizophrenia in the Japanese population. J Neural Transm 115, 1457–1461 (2008). https://doi.org/10.1007/s00702-008-0114-8

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  • DOI: https://doi.org/10.1007/s00702-008-0114-8

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