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Molecular neurobiology
08, 2016;53 (6): 3967-3975.

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

Shanshan Shao, Rui Kong, Li Zou, Rong Zhong, Jiao Lou, Jie Zhou, Shengnan Guo, Jia Wang, Xiaohui Zhang, Jiajia Zhang, Ranran Song
Author Information
  1. Shanshan Shao: 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.
  2. Rui Kong: 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.
  3. Li Zou: Department of Health Care, Baoan Maternal and Child Health Hospital, Shenzhen, 518100, China.
  4. Rong Zhong: 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.
  5. Jiao Lou: 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.
  6. Jie Zhou: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA.
  7. Shengnan Guo: 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.
  8. Jia Wang: 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.
  9. Xiaohui Zhang: 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.
  10. Jiajia Zhang: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA.
  11. Ranran Song: 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. songranran@hust.edu.cn.
PMID: 26184631 DOI: 10.1007/s12035-015-9334-8

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.

Keywords

DOCK4 Developmental dyslexia KIAA0319 KIAA0319L Neurite outgrowth Neuronal migration

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MeSH Term

Cell Movement
Child
Dyslexia
Epistasis, Genetic
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Nerve Net
Neuronal Outgrowth
Neurons
Polymorphism, Single Nucleotide
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0DDrs207413095 %P = 0variantsrs28366021rs4504469riskmigrationKIAA0319LKIAA0319DOCK4CI = 1CCGGneuritedyslexiaoutgrowthnetworkobservedsignificantly = 0OR = 1amongrs2274305combinationgenotypeindividualsCTTTOR = 2000NeuronalNeuriteDevelopmentalAbnormalregulationneuralgrowththoughtimportantfeaturedevelopmentalinvestigated16geneticselectedbioinformaticsanalysessixkeygenesneuronalChinesepopulationfirstassociatedfalsediscoveryrateFDRadjustmentmultiplecomparisonsoddsratioOR672confidenceintervalCI505-0894006608174-2203003681203-2348002followingclassificationregressiontreeCARTanalysisrevealedpredictionvaluegene-geneinteractionsDCDC2Comparedlowestcarrierscarryingcombinedgenotypesincreased492447-4290001exhibitedhighest770CI = 2265-6276significantdoseeffectfourPtrend = 0summarystudysupportsimportancesingle-multiple-risksusceptibilityChinaRolesGenesMigrationOutgrowthNetworkDyslexia:Single-Multiple-RiskGeneticVariants

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