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The Roles of Genes in the Neuronal Migration and Neurite Outgrowth Network in Developmental Dyslexia: Single- and Multiple-Risk Genetic Variants

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Abstract

Abnormal regulation of neural migration and neurite growth is thought to be an important feature of developmental dyslexia (DD). We investigated 16 genetic variants, selected by bioinformatics analyses, in six key genes in the neuronal migration and neurite outgrowth network in a Chinese population. We first observed that KIAA0319L rs28366021, KIAA0319 rs4504469, and DOCK4 rs2074130 were significantly associated with DD risk after false discovery rate (FDR) adjustment for multiple comparisons (odds ratio (OR) = 0.672, 95 % confidence interval (CI) = 0.505–0.894, P = 0.006; OR = 1.608, 95 % CI = 1.174–2.203, P = 0.003; OR = 1.681, 95 % CI = 1.203–2.348, P = 0.002). The following classification and regression tree (CART) analysis revealed a prediction value of gene-gene interactions among DOCK4 rs2074130, KIAA0319 rs4504469, DCDC2 rs2274305, and KIAA0319L rs28366021 variants. Compared with the lowest risk carriers of the combination of rs2074130 CC, rs4504469 CC, and rs2274305 GG genotype, individuals carrying the combined genotypes of rs2074130 CC, rs4504469 CT or TT, and rs28366021 GG had a significantly increased risk for DD (OR = 2.492, 95 % CI = 1.447–4.290, P = 0.001); individuals with the combination of rs2074130 CT or TT and rs28366021 GG genotype exhibited the highest risk for DD (OR = 2.770, 95 % CI = 2.265–6.276, P = 0.000). A significant dose effect was observed among these four variants (P for trend = 0.000). In summary, this study supports the importance of single- and multiple-risk variants in this network in DD susceptibility in China.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China NSFC-81273092; the Fundamental Research Funds for the Central Universities (HUST: 2014TS053); and project from Health and Family Planning Commission of Hubei Province (WJ2015MB019).

Conflict of Interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Maternal and Child Health and MOE (Ministry of Education) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Shanshan Shao, Rui Kong, Shengnan Guo, Jia Wang, Xiaohui Zhang & Ranran Song

  2. Department of Health Care, Baoan Maternal and Child Health Hospital, Shenzhen, 518100, China

    Li Zou

  3. Department of Epidemiology and Biostatistics and MOE (Ministry of Education) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Rong Zhong & Jiao Lou

  4. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA

    Jie Zhou & Jiajia Zhang

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  1. Shanshan Shao
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  2. Rui Kong
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Shao, S., Kong, R., Zou, L. et al. The Roles of Genes in the Neuronal Migration and Neurite Outgrowth Network in Developmental Dyslexia: Single- and Multiple-Risk Genetic Variants. Mol Neurobiol 53, 3967–3975 (2016). https://doi.org/10.1007/s12035-015-9334-8

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