title: The Roles of Genes in the Neuronal Migration and Neurite Outgrowth Network in Developmental Dyslexia: Single- and Multiple-Risk Genetic Variants.
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.
authors.affiliation: 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.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Health Care, Baoan Maternal and Child Health Hospital, Shenzhen, 518100, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ranran
authors.initials: R
authors.lastname: Song
mesh_terms: D002465:Cell Movement / Q000235:genetics*; D002648:Child; D004410:Dyslexia / Q000235:genetics* / Q000473:pathology*; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology*; D000071446:Neuronal Outgrowth / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: DOCK4; Developmental dyslexia; KIAA0319; KIAA0319L; Neurite outgrowth; Neuronal migration