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Axon guidance pathway genes are associated with schizophrenia risk.

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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6257106 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Axon guidance pathway genes are associated with schizophrenia risk.

Wang Zhichao Z Li Ping P Wu Tong T Zhu Shuangyue S Deng Libin L Cui Guangcheng G

Experimental and therapeutic medicine 20180919 6

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<sup>-3</sup>). Moreover, 15 ...[more]

PMID: 30542400

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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis

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Axon guidance pathway genes are associated with schizophrenia risk.

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Axon guidance pathway genes are associated with schizophrenia risk.

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