NRG1 ), d -amino acid oxidase ( DAO ), and DAO activator ( DAOA )/ G72 polymorphisms with schizophrenia

摘要

Abstract The glutamate hypothesis of schizophrenia is related to the proposed dysregulation of d -amino acid oxidase ( DAO ), DAO activator ( DAOA )/ G72 , and Neuregulin 1 ( NRG1 ) genes. Genetic studies have shown significant associations between DAO , DAOA , NRG1 single-nucleotide polymorphisms (SNPs), and schizophrenia. The systematic literature search yielded 6, 5, and 18 new studies for DAO , DAOA , and NRG1 published after 2011 and not included in the previous SchizophreniaGene (SZGene) meta-analysis. We conducted meta-analyses of 20, 23, and 48 case–control studies, respectively, to comprehensively evaluate the association of 8 DAO , 12 DAOA , and 14 NRG1 SNPs with schizophrenia. The updated meta-analyses resulted in the following findings: the C-allele of DAO rs4623951 was associated with schizophrenia across all pooled studies [Odds ratio (OR)?=?0.88, 95% confidence interval (CI)?=?0.79–0.98, p ?=?0.02, N ?=?3143]; however, no new reports could be included. The G-allele of DAOA rs778293 was associated with schizophrenia in Asian patients (OR?=?1.17, 95% CI?=?1.08–1.27, p ?=?0.00008, N ?=?6117), and the T-allele of DAOA rs3916971 was associated with schizophrenia across all studies (OR?=?0.84, 95% CI?=?0.73–0.96, p ?=?0.01, N?=?1765). Again, for both SNPs, no new eligible studies were available. After adding new reports, the T-allele of NRG1 SNP8NRG241930 (rs62510682) across all studies (OR?=?0.95, 95% CI?=?0.91–0.997, p ?=?0.04, N ?=?22,898) and in Caucasian samples (OR?=?0.95, 95% CI?=?0.90–0.99, p ?=?0.03, N ?=?16,014), and the C-allele of NRG1 rs10503929 across all studies (OR?=?0.89, 95% CI?=?0.81–0.97, p ?=?0.01, N ?=?6844) and in Caucasian samples (OR?=?0.89, 95% CI?=?0.81–0.98, p ?=?0.01, N ?=?6414) were protective against schizophrenia. Our systematic meta-analysis is the most updated one for the association of DAO , DAOA , and NRG1 SNPs with schizophrenia.