Cognitive impairment is one of the core symptoms of schizophrenia. Multiple domains of cognition are affected in patients with schizophrenia, which has a major effect on the functional outcome. Recent studies indicate that SNPs in the gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2) gene are associated with the risk of schizophrenia, however, the effect of these SNPs on cognitive function in patients with schizophrenia has not been explored. In this study, we first performed a case–control analysis of three SNPs (rs187269 allele A vs. G, rs252944 allele C vs. G, and rs194072 allele A vs. G) in 100 patients and 90 controls, then conducted a meta-analysis and found the SNP rs194072 was associated with schizophrenia (OR = 0.86, P = 0.0119), and survived after Bonferroni correction. The haplotype analysis suggested that the haplotype ACA, comprising the three SNPs (rs187269, rs252944 and rs194072) was also significantly associated with schizophrenia (P = 0.049).Then, we performed an association analysis of three SNPs (rs187269, rs252944 and rs194072) in GABRB2 gene with cognitive performance in patients with first episode schizophrenia. We found that the allele G of rs187269 in the GABRB2 gene was significantly associated with better cognitive flexibility (P = 0.005), a major aspect of executive function, in patients with first episode schizophrenia. The haplotype ACA was significantly associated with cognitive flexibility in patients with schizophrenia (P = 0.023). Our study showed that SNPs in GABRB2 may have a significant effect on cognitive function in patients with schizophrenia, suggesting that modulating GABRB2 may have therapeutic potential to improve cognitive function of patients with schizophrenia.
GABRB2SNPs Schizophrenia Cognitive function
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QZ, XZ, SS and HH performed the cognitive test in patients and collected the blood samples; QZ and XW performed DNA extraction and amplification experiments; HY, SW and XZ analyzed the data; QZ, HY, and SW wrote the paper. GL and YW conceived the experiments and wrote the paper. All authors reviewed the manuscript.
The present work was funded by National Natural Science Foundation of China (No. 81571334 and No. 81771147), Natural Science Foundation of Shandong Province (ZR2011HM023, ZR2016HM30), research project of teaching reform in undergraduate colleges and universities in Shandong Province(2015M049), the development of medical science and technology project of Shandong Province(2011HZ011), science and technology project of higher education of Shandong Province(J10LF01) and postgraduate education innovation program of Shandong Province(SDYY15012).
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