Chitinase-3-like 1 (CHI3L1) gene and schizophrenia: genetic association and a potential functional mechanism.
BACKGROUND
Gene expression data and association analyses in two Chinese samples implicate chitinase 3-like 1 (CHI3L1), a cellular survival gene, in schizophrenia susceptibility.


METHODS
We tested whether the association data are robust to replication in a Caucasian schizophrenia sample and performed a comprehensive investigation of common genetic variation at the locus.


RESULTS
In a sample of 375 case and 812 control subjects we identified significant association with the same risk allele at the promoter single nucleotide polymorphism (SNP) associated in the original study (rs10399805; p = .018) and with another SNP at intron 7 of CHI3L1 (rs2275351; p = .008). The rs10399805 SNP is located at position -247 and disrupts the C/EBP-AML-1 binding site in the gene promoter; the risk allele is predicted to increase CHI3L1 expression, as has been reported in several postmortem schizophrenia studies. Carriers of the risk variant presented with fewer positive symptoms and relatively spared cognitive performance compared with other schizophrenia patients.


CONCLUSIONS
These findings support a functional mechanism for involvement of CHI3L1 in schizophrenia susceptibility, possibly contributing to a less severe illness. The associated variants in this study are not well tagged by all Whole-Genome Association (WGA) platforms, suggesting additional genotyping may be necessary despite the imminent availability of WGA data from large SZ samples. Because CHI3L1 may be involved in transmission of stress-induced cellular responses, studies of interaction with known environmental risk factors may also be warranted.
Yang
Mao Sheng
MS
Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Ireland.
Morris
Derek W
DW
Donohoe
Gary
G
Kenny
Elaine
E
O'Dushalaine
Colm T
CT
Schwaiger
Siobhan
S
Nangle
Jeanne Marie
JM
Clarke
Sarah
S
Scully
Paul
P
Quinn
John
J
Meagher
David
D
Baldwin
Patrizia
P
Crumlish
Niall
N
O'Callaghan
Eadbhard
E
Waddington
John L
JL
Gill
Michael
M
Corvin
Aiden
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D054392:Adipokines; D000483:Alleles; D044466:Asian People / Q000235:genetics* / Q000523:psychology; D002470:Cell Survival / Q000235:genetics; D000071451:Chitinase-3-Like Protein 1; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D003431:Cross-Cultural Comparison; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D037102:Lectins; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D016601:RNA-Binding Proteins / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D012565:Schizophrenic Psychology; D012931:Social Environment; D044465:White People / Q000235:genetics / Q000523:psychology
D048868:Adaptor Proteins, Signal Transducing; D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D050676:Core Binding Factor Alpha 2 Subunit; D006023:Glycoproteins; D037102:Lectins; C101633:PA2G4 protein, human; D016601:RNA-Binding Proteins; C493728:RUNX1 protein, human