The chitinase 3-like 1 gene and schizophrenia

Evidence from a multi-center case-control study and meta-analysis

Kazutaka Ohi, Ryota Hashimoto, Yuka Yasuda, Tetsuhiko Yoshida, Hidetoshi Takahashi, Naomi Iike, Masao Iwase, Kouzin Kamino, Ryouhei Ishii, Hiroaki Kazui, Motoyuki Fukumoto, Hironori Takamura, Hidenaga Yamamori, Michiyo Azechi, Koji Ikezawa, Hitoshi Tanimukai, Shinji Tagami, Takashi Morihara, Masayasu Okochi, Kazuo Yamada & 10 others Shusuke Numata, Masashi Ikeda, Toshihisa Tanaka, Takashi Kudo, Shu ichi Ueno, Takeo Yoshikawa, Tetsuro Ohmori, Nakao Iwata, Norio Ozaki, Masatoshi Takeda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in response to several environmental and psychosocial stresses. The expression level of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of patients with schizophrenia. Genetic variants of the CHI3L1 gene have been significantly associated with schizophrenia in two distinct ethnic groups, the Chinese and Irish populations. The aims of this study are to confirm the association between the CHI3L1 gene and schizophrenia in a Japanese population using the largest sample size to date (1463 cases and 1795 controls) and perform a meta-analysis of the combined samples (3005 cases, 3825 controls and 601 trios). We found significant associations between single nucleotide polymorphism (SNP) 4/rs4950928 (p = 0.009), which is located in the promoter region of the CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most significant global p < 0.001). As the meta-analysis of the combined samples showed significant heterogeneity among studies of SNP3/rs10399805 (p = 0.026) and SNP4 (p < 0.001), we performed meta-analyses separately in the Japanese (2033 cases and 2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios), the major groups analyzed in association studies of the CHI3L1 gene. The meta-analysis in Japanese populations showed stronger evidence for the association of schizophrenia with SNP4 (p = 0.003), while the meta-analysis in Chinese populations showed an association with a different variant (SNP3) (p = 0.003). We conclude that the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a susceptibility to schizophrenia in Asian populations.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalSchizophrenia Research
Volume116
Issue number2-3
DOIs
Publication statusPublished - 01-02-2010

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Chitinases
Meta-Analysis
Case-Control Studies
Schizophrenia
Genes
Population
Single Nucleotide Polymorphism
Prefrontal Cortex
Ethnic Groups
Genetic Promoter Regions
Sample Size
Haplotypes
Hippocampus
Survival

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Ohi, K., Hashimoto, R., Yasuda, Y., Yoshida, T., Takahashi, H., Iike, N., ... Takeda, M. (2010). The chitinase 3-like 1 gene and schizophrenia: Evidence from a multi-center case-control study and meta-analysis. Schizophrenia Research, 116(2-3), 126-132. https://doi.org/10.1016/j.schres.2009.12.002
Ohi, Kazutaka ; Hashimoto, Ryota ; Yasuda, Yuka ; Yoshida, Tetsuhiko ; Takahashi, Hidetoshi ; Iike, Naomi ; Iwase, Masao ; Kamino, Kouzin ; Ishii, Ryouhei ; Kazui, Hiroaki ; Fukumoto, Motoyuki ; Takamura, Hironori ; Yamamori, Hidenaga ; Azechi, Michiyo ; Ikezawa, Koji ; Tanimukai, Hitoshi ; Tagami, Shinji ; Morihara, Takashi ; Okochi, Masayasu ; Yamada, Kazuo ; Numata, Shusuke ; Ikeda, Masashi ; Tanaka, Toshihisa ; Kudo, Takashi ; Ueno, Shu ichi ; Yoshikawa, Takeo ; Ohmori, Tetsuro ; Iwata, Nakao ; Ozaki, Norio ; Takeda, Masatoshi. / The chitinase 3-like 1 gene and schizophrenia : Evidence from a multi-center case-control study and meta-analysis. In: Schizophrenia Research. 2010 ; Vol. 116, No. 2-3. pp. 126-132.
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Ohi, K, Hashimoto, R, Yasuda, Y, Yoshida, T, Takahashi, H, Iike, N, Iwase, M, Kamino, K, Ishii, R, Kazui, H, Fukumoto, M, Takamura, H, Yamamori, H, Azechi, M, Ikezawa, K, Tanimukai, H, Tagami, S, Morihara, T, Okochi, M, Yamada, K, Numata, S, Ikeda, M, Tanaka, T, Kudo, T, Ueno, SI, Yoshikawa, T, Ohmori, T, Iwata, N, Ozaki, N & Takeda, M 2010, 'The chitinase 3-like 1 gene and schizophrenia: Evidence from a multi-center case-control study and meta-analysis', Schizophrenia Research, vol. 116, no. 2-3, pp. 126-132. https://doi.org/10.1016/j.schres.2009.12.002

The chitinase 3-like 1 gene and schizophrenia : Evidence from a multi-center case-control study and meta-analysis. / Ohi, Kazutaka; Hashimoto, Ryota; Yasuda, Yuka; Yoshida, Tetsuhiko; Takahashi, Hidetoshi; Iike, Naomi; Iwase, Masao; Kamino, Kouzin; Ishii, Ryouhei; Kazui, Hiroaki; Fukumoto, Motoyuki; Takamura, Hironori; Yamamori, Hidenaga; Azechi, Michiyo; Ikezawa, Koji; Tanimukai, Hitoshi; Tagami, Shinji; Morihara, Takashi; Okochi, Masayasu; Yamada, Kazuo; Numata, Shusuke; Ikeda, Masashi; Tanaka, Toshihisa; Kudo, Takashi; Ueno, Shu ichi; Yoshikawa, Takeo; Ohmori, Tetsuro; Iwata, Nakao; Ozaki, Norio; Takeda, Masatoshi.

In: Schizophrenia Research, Vol. 116, No. 2-3, 01.02.2010, p. 126-132.

Research output: Contribution to journalArticle

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T1 - The chitinase 3-like 1 gene and schizophrenia

T2 - Evidence from a multi-center case-control study and meta-analysis

AU - Ohi, Kazutaka

AU - Hashimoto, Ryota

AU - Yasuda, Yuka

AU - Yoshida, Tetsuhiko

AU - Takahashi, Hidetoshi

AU - Iike, Naomi

AU - Iwase, Masao

AU - Kamino, Kouzin

AU - Ishii, Ryouhei

AU - Kazui, Hiroaki

AU - Fukumoto, Motoyuki

AU - Takamura, Hironori

AU - Yamamori, Hidenaga

AU - Azechi, Michiyo

AU - Ikezawa, Koji

AU - Tanimukai, Hitoshi

AU - Tagami, Shinji

AU - Morihara, Takashi

AU - Okochi, Masayasu

AU - Yamada, Kazuo

AU - Numata, Shusuke

AU - Ikeda, Masashi

AU - Tanaka, Toshihisa

AU - Kudo, Takashi

AU - Ueno, Shu ichi

AU - Yoshikawa, Takeo

AU - Ohmori, Tetsuro

AU - Iwata, Nakao

AU - Ozaki, Norio

AU - Takeda, Masatoshi

PY - 2010/2/1

Y1 - 2010/2/1

N2 - The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in response to several environmental and psychosocial stresses. The expression level of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of patients with schizophrenia. Genetic variants of the CHI3L1 gene have been significantly associated with schizophrenia in two distinct ethnic groups, the Chinese and Irish populations. The aims of this study are to confirm the association between the CHI3L1 gene and schizophrenia in a Japanese population using the largest sample size to date (1463 cases and 1795 controls) and perform a meta-analysis of the combined samples (3005 cases, 3825 controls and 601 trios). We found significant associations between single nucleotide polymorphism (SNP) 4/rs4950928 (p = 0.009), which is located in the promoter region of the CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most significant global p < 0.001). As the meta-analysis of the combined samples showed significant heterogeneity among studies of SNP3/rs10399805 (p = 0.026) and SNP4 (p < 0.001), we performed meta-analyses separately in the Japanese (2033 cases and 2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios), the major groups analyzed in association studies of the CHI3L1 gene. The meta-analysis in Japanese populations showed stronger evidence for the association of schizophrenia with SNP4 (p = 0.003), while the meta-analysis in Chinese populations showed an association with a different variant (SNP3) (p = 0.003). We conclude that the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a susceptibility to schizophrenia in Asian populations.

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