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Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study

Molecular Neurobiology volume 54, pages 3162–3179 (2017)Cite this article

An Erratum to this article was published on 04 May 2016

Abstract

Although lots of genes have been revealed to relate to sporadic amyotrophic lateral sclerosis (sALS), its genetic mechanisms still need to be further explored. We aimed to search the novel genetic factors of sALS and assess their contribution. We constructed an integrative dataset based on the 3227 subsignificant genes (P value < 0.01) from two sALS-related genome-wide association studies (GWAS) (the US and Irish studies). A significant replication between both studies was confirmed by the gene set enrichment analysis in the integral level (P value < 10−4). Using the pathway overrepresentation analysis, we revealed the 34 shared Gene Ontology (GO) biological processes from the two independent studies (P value < 0.01). Among these pathways, the nervous system developmental pathway (NSD function, GO:0007399) was further supported by the previously reported genes related to sALS (P value = 3.28e−12). Importantly, four of 17 NSD-function-related target genes (disrupted-in-schizophrenia-1 (DISC1), CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case–control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles.

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Abbreviations

sALS:

Sporadic amyotrophic lateral sclerosis

GWAS:

Genome-wide association studies

GO:

Gene Ontology

CHPM:

Chinese Han population from mainland

NSD:

Nervous system development

DISC1:

Disrupted-in-schizophrenia-1

CNTN4:

Contactin 4

NRXN3:

Neurexin 3

OR:

Odds ratio

FPRP:

False-positive report probabilities

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Acknowledgments

We are grateful to the sALS patients who generously contributed their time and materials for this research.

Author information

Author notes

    Affiliations

    1. Department of Neurology, the first affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

      Jie Zhang, Xin Fang & Renshi Xu

    2. Institute of Translational Medicine, Nanchang University, Nanchang, 330031, Jiangxi, China

      Libin Deng & Zhujun Cheng

    3. College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China

      Libin Deng, Jie Zhang, Xiaoli Tang & Gang Li

    4. School of Public Health, Nanchang University, Nanchang, 330006, Jiangxi, China

      Liwei Hou

    5. Deparment of Vasculocardiology, the second affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

      Jinsong Xu

    6. Department of Neurology, Guangdong General hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, 510080, China

      Xiong Zhang

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    1. Libin Deng
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    Correspondence to Xiong Zhang or Renshi Xu.

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    Authorship

    R.X., L.D., and X.Z. conceived and designed the experiments. L.D., L.H., J.Z., X.T., Z.C., G.L., X.F., and J.X. performed the experiments. R.X., L.H., and L.D. analyzed the data. X.Z. contributed partial materials. R.X. and L.D. wrote the paper.

    Conflict of Interest

    The authors declare that they have no conflict of interest.

    Funding

    The work was funded by grants from the National Natural Science Foundation of China (grant numbers 30560042, 81160161, 81360198, 81260021, 81200631, and 30871384), the Education Department of Jiangxi Province (grant numbers [2005(183)], GJJ13091, 20132BAB205060, 20133BCB23007, and cx2015183), Guangdong Provincial Science and Technology Project Foundation (grant number 2012B031800410), and the Jiangxi Provincial Department of Science and Technology (grant number [2014]-47), China.

    Additional information

    Libin Deng and Liwei Hou were joint first authors.

    Libin Deng, Liwei Hou and Jie Zhang contributed equally to this work.

    An erratum to this article is available at http://dx.doi.org/10.1007/s12035-016-9897-z.

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    Deng, L., Hou, L., Zhang, J. et al. Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study. Mol Neurobiol 54, 3162–3179 (2017). https://doi.org/10.1007/s12035-016-9869-3

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    Keywords

    • Sporadic amyotrophic lateral sclerosis
    • Nervous system developmental pathway
    • DISC1 gene