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. 2018 Dec;16(6):4519-4526.
doi: 10.3892/etm.2018.6781. Epub 2018 Sep 19.

Axon guidance pathway genes are associated with schizophrenia risk

Zhichao Wang  1 , Ping Li  2 , Tong Wu  2 , Shuangyue Zhu  3 , Libin Deng  4 , Guangcheng Cui  2
Affiliations

Axon guidance pathway genes are associated with schizophrenia risk

Zhichao Wang et al. Exp Ther Med. 2018 Dec.

Abstract

In the present study, we analyzed schizophrenia (SCZ)-related genome-wide association studies (GWAS) to identify genes and pathways associated with SCZ. We identified 1,098 common genes (1,098/9,468) and 20 shared KEGG pathways (both P<0.01) by integrating candidate genes from the European and American SCZ-related GWAS. The pathways related to axon guidance, long term potentiation and arrhythmogenic right ventricular cardiomyopathy (ARVC) were highly significant (P<10-3). Moreover, 15 axon guidance pathway-related genes were associated with SCZ. The association between axon guidance pathway genes and SCZ was validated by a two-stage case-control study on Shandong migrants in northeastern China. Moreover, individuals with the rs9944880 TT polymorphism in the deleted in colorectal cancer (DCC) gene were associated with SCZ. These findings indicate that the axon guidance pathway genes and the rs9944880 SNP in DCC gene are associated with SCZ pathogenesis.

Keywords: Gene Set Enrichment Analysis; axon guidance; genome-wide association study; schizophrenia.

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Figures

Figure 1.
Figure 1.
Ranks of significant genes in the American and European GWAS. GSEA of candidate genes (A) in the European GWAS associated with SCZ in the American GWAS and (B) in the American GWAS associated with SCZ in the European GWAS. (C) The common SCZ-related pathways in the European and American GWAS. GWAS, genome-wide association studies; GSEA, Gene Set Enrichment Analysis; SCZ, schizophrenia.
Figure 2.
Figure 2.
Ranks of significant genes in the pooled GWAS dataset. (A) Axon guidance pathway genes enriched in the pooled GWAS. (B) Fifteen significant axon guidance pathway-related genes identified in this study. (C) Common SCZ susceptibility pathways in the SCZ meta-analysis, European and American datasets. GWAS, genome-wide association studies; SCZ, schizophrenia.
Figure 3.
Figure 3.
The common axon guidance-related genes from European, American and SCZ meta-analysis datasets. SCZ, schizophrenia.
See this image and copyright information in PMC

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