TY - JOUR
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
N1 - Funding Information:
This work was funded in part by grants-in-aid from the Japanese Ministry of Health, Labor and Welfare ( H18-kokoro-005 , H19-kokoro-002 ), the Japanese Ministry of Education, Culture, Sports, Science and Technology ( 18689030 ), CREST of JST , Grant-aid for Scientific Research on Priority Areas — Research on Pathomechanisms of Brain Disorders — from the MEXT ( 18023045 ) and Japan Foundation for Neuroscience and Mental Health . The study sponsors had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2010/2
Y1 - 2010/2
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.
AB - 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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U2 - 10.1016/j.schres.2009.12.002
DO - 10.1016/j.schres.2009.12.002
M3 - Article
C2 - 20051317
AN - SCOPUS:74849098503
SN - 0920-9964
VL - 116
SP - 126
EP - 132
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 2-3
ER -
