title: The chitinase 3-like 1 gene and schizophrenia: evidence from a multi-center case-control study and meta-analysis.
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.
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Iike
authors.forename: Masao
authors.initials: M
authors.lastname: Iwase
authors.forename: Kouzin
authors.initials: K
authors.lastname: Kamino
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Ishii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kazui
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Takamura
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.forename: Michiyo
authors.initials: M
authors.lastname: Azechi
authors.forename: Koji
authors.initials: K
authors.lastname: Ikezawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanimukai
authors.forename: Shinji
authors.initials: S
authors.lastname: Tagami
authors.forename: Takashi
authors.initials: T
authors.lastname: Morihara
authors.forename: Masayasu
authors.initials: M
authors.lastname: Okochi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: 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
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins