The chitinase 3-like 1 gene and schizophrenia: evidence from a multi-center case-control study and meta-analysis.
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.
Ohi
Kazutaka
K
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hashimoto
Ryota
R
Yasuda
Yuka
Y
Yoshida
Tetsuhiko
T
Takahashi
Hidetoshi
H
Iike
Naomi
N
Iwase
Masao
M
Kamino
Kouzin
K
Ishii
Ryouhei
R
Kazui
Hiroaki
H
Fukumoto
Motoyuki
M
Takamura
Hironori
H
Yamamori
Hidenaga
H
Azechi
Michiyo
M
Ikezawa
Koji
K
Tanimukai
Hitoshi
H
Tagami
Shinji
S
Morihara
Takashi
T
Okochi
Masayasu
M
Yamada
Kazuo
K
Numata
Shusuke
S
Ikeda
Masashi
M
Tanaka
Toshihisa
T
Kudo
Takashi
T
Ueno
Shu-Ichi
S
Yoshikawa
Takeo
T
Ohmori
Tetsuro
T
Iwata
Nakao
N
Ozaki
Norio
N
Takeda
Masatoshi
M
D054392:Adipokines; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D003431:Cross-Cultural Comparison; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins