| We aim to conduct a systematic study of the epidemiology, genetic factors and gene-environment interactions of developmental dyslexia (DD) to lay academic foundations for prevention, diagnosis and intervention of this disorder.Part 1 An epidemiological survey and associated factors analysis of Chinese dyslexic children in four cities/counties, Hubei ProvinceObjective:We aim to learn about the prevalence and the distribution of DD in Hubei Province, and explore the epidemiological characteristics and environmental factors for DD in China.Methods:Using cluster sampling, we selected 46 schools from four cities/ counties and investigated 25,150 students (19,844 were valid) from grade 3rd to 6th. We conducted chi-square test and Cochran-Armitage trend test to analyze the data.Results:The overall prevalence of DD was 3.6%, and it was significantly higher in boys than in girls (χ2= 254.02, P< 0.001). According to the P-values in the chi-square test, there were significant differences in the distributions of dyslexic children in the socioeconomic status (SES, including monthly income and parental education) and the home literacy environment (HLE, including whether child participates in extracurricular activity such as reading? Does child study actively? Whether child has scheduled reading time every day? The frequency of parents reading; How often do parents buy new books for child? How much do parents spend on books for child every year? The frequency of parents reading books to child since childhood; Do parents encourage child to read books? Do parents buy the books which child was interested in?). The Cochran-Armitage trend test indicated significantly trends with the prevalence of DD being decreased with increasing SES and HLE levels (all the P for trend were less than 0.001).Conclusion:There are significantly differences in the distributions of gender, SES and HLE of dyslexic children in China, indicating that these might be the risk factors for DD in China.Part 2. The roles of genes in the neuronal migration and neurite outgrowth network in DD:single-and multiple-risk genetic variantsObjective:To explore the associations between genetic variants in the neuronal migration and neurite outgrowth network and DD risk, and find genetic risk factors for DD in China.Methods:Sixteen genetic variants in six key genes (DYX1C1, DCDC2, KIAA0319, ROBO1, KIAA0319L and DOCK4) in the neuronal migration and neurite outgrowth network were genotyped in 409 dyslexic children and 410 normal readers. Then, we used logistic regression analysis, classification and regression tree (CART) analysis, and cumulative effect analysis to analyze the data.Results:(1) On univariant logistic regression analysis, we observed that KIAA0319L rs28366021, KIAA0319 rs4504469 and DOCK4 rs2074130 were significantly associated with DD risk after false discovery rate (FDR) adjustment for multiple comparisons (OR= 0.67,95% CI= 0.51-0.89; OR= 1.61,95% CI= 1.17-2.20; OR= 1.68,95% CI= 1.20-2.35).(2) The following 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= 2.29,95% CI= 1.39-3.77); individuals with the combination of rs2074130 CT or TT and rs28366021 GG genotype exhibited the highest risk for DD (OR= 2.98,95% CI= 1.87-4.75).(3) A cumulative effect of the 4 SNPs identified in the CART analysis was evaluated by logistic regression analysis. Compared with the 0-2 risk alleles subgroup, both of the subgroups with 3-4 risk alleles and 5-7 risk alleles showed significant associations with increased DD risk (OR= 1.60,95% CI= 1.19-2.15; OR = 2.74,95%CI= 1.42-5.32), controlling for age and gender. The Cochran-Armitage trend test indicated a significant dose effect with the ORs being increased with increasing numbers of risk alleles (P for trend <0.001).Conclusion:In summary, this study supports the importance of single-and multiple-risk variants in this network in DD susceptibility in China.Part 3. A priliminary discussion for interactions between SES, HLE and genetic variants in the neuronal migration and neurite outgrowth network of DD in ChinaObjective:Based on the above two parts, we aim to further discuss the gene-environment interactions of DD in China in this part.Methods:Multivariate logistic regression analysis was used to explore the interactions between SES, HLE and risk genetic variants in the neuronal migration and neurite outgrowth network.Results:Before FDR adjustment, marginally significant interaction was observed between parental education and KIAA0319L rs28366021 in modulation of DD risk (Pinteraction=0.048). The frequency of parents reading showed significantly pair-wise interaction with KIAA0319L rs28366021 (Pinteraction=0.023). The models of gene-environment interactions were all bioeco logical. After FDR adjustment, both P values for interactions were greater than 0.05.Conclusion:There might be gene-environment interactions in DD susceptibility, and bioecological interaction model is suggested. However, the result should be treated with caution because of the presence of false positive from multiple comparisons. |
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