Research On Genetic Susceptibility,Home Environment,and G-E Interaction To Chinese Dyslexia

Based on epidemiological survey and study on susceptible genes screened by bioinformatics tools,we aimed to explore the potential influence factors of dyslexia from environmental,genetic,and gene-environment interaction aspects which could provide the foundation for detection,diagnose,and intervention.Part 1 Descriptive epidemiology of prenatal and perinatal risk factors in a Chinese population with dyslexiaObjective:Our aim was to screen prenatal and perinatal factors and elucidate the distribution of dyslexia in Chinese.Methods:A total of 45,850 students were recruited from grades three to six in 84primary schools,from seven cities of Hubei province using cluster sampling.Dyslexia in Chinese was diagnosed based on the score of Dyslexia Checklist for Chinese Children?DCCC?and Pupil Rating Scale Revised Screening for Learning?PRS?.The performance on Chinese language exam was also considered.Questionnaires about home environmental factors were completed by parent or guardian.Chi-square test and logistic regression analysis were used to analyze the data.Results:?1?Among the 34,748 eligible participants,1,200?3.45%?were diagnosed with dyslexia in Chinese.More boy suffered from dyslexia than girl,and the gender ratio was 3:1.There was a downward trend between dyslexia and grades?P for trend<0.05?.The distribution of dyslexic children was different from non-dyslexic children on SES indicators including parents'education level,parent'occupation,and family income?P<0.05?.?2?After adjustment for possible confounding variables,the risk of dyslexia was significantly associated with maternal infectious diseases?OR=1.59,95%CI=1.25–2.03?,preterm birth?OR=1.30,95%CI=1.01–1.66?,difficult vaginal delivery?OR=1.58,95%CI=1.03–2.42?,and neonatal asphyxia?OR=2.38,95%CI=1.61–3.52?.Conclusion:Chinese dyslexia is fairly pervasive in primary school students.Maternal infectious diseases,difficult vaginal delivery,preterm birth,and neonatal asphyxia may increase the risk of developmental dyslexia in China.Part 2 Research on the genetic susceptibility to dyslexia in Chinese based on candidate gene strategy and GWAS strategyObjective:Our aim was to explore the genetic risk factors of dyslexia in Chinese based on candidate gene strategy and GWAS strategy.Methods:We screened candidate genes based on text mining and protein-protein interaction network.GWAS SNPs were screened based on expression quantitative trait loci?eQTL?analyses and neuroimaging replication.Two dyslexia candidate genes?CNTNAP2 and FOXP2?,three SNPs?rs349045,rs201605,rs4234898?and two genes?ZNF385D and RBFOX2?from GWAS were genotyped in 372 dyslexic children and354 controls.Logistic regression was used to analyze the association between SNPs and the risk of dyslexia.Linear regression was used to analyze the association between SNPs and the symptoms of dyslexia.Multifactor dimensionality reduction was used to analyze the SNP-SNP interaction.Results:?1?The results of logistic regression showed that CNTNAP2 rs3779031and ZNF385D rs4858399 were significantly associated with the risk of dyslexia?OR=0.546,95%CI=0.324–0.919;OR=1.29,95%CI=1.035–1.607?.After FDR adjustment for multiple comparisons,the associations were nonsignificant.?2?The results of linear regression showed that CNTNAP2 rs2462603 was associated with bad reading habits?B=-2.277,P=0.019?;CNTNAP2 rs9648691 was associated with deficit of written expression?B=1.863,P=0.038?and auditory deficits of words recognition?B=2.322,P=0.018?;MYH3 rs201605 was associated with bad reading habits?B=2.160,P=0.027?and deficit of spelling?B=1.982,P=0.025?;CTSO rs4234898 was associated with deficit in oral language?B=2.673,P=0.020?;ZNF385D rs12636438 and ZNF385D rs1679255 were associated with deficit in oral language?B=2.717,P=0.009;B=2.761,P=0.011?.?3?The results of MDR showed that there was an interaction among FOXP2rs1058335,ZNF385D rs1679255,and CNTNAP2 rs987456.Conclusion:CNTNAP2 rs3779031 and ZNF385D rs4858399 may play role in dyslexia susceptibility.CNTNAP2 may relate with several dyslexia symptoms and ZNF385D may contribute to oral language deficit in dyslexic children.Part 3 Interactions between CNTNAP2,ZNF385D and home environment in Chinese dyslexiaObjective:Our aim was to explore the gene-environment interaction based on the results from the above two parts.Methods:Multivariate logistic regression was used to analyze the interaction between genes?CNTNAP2,ZNF385D?and home environment factors including SES,HLE,prenatal and perinatal factors in a case-control study.Results:The results of multivariate logistic regression showed that CNTNAP2rs3779031 significantly interacted with maternal occupation,paternal education level,parents telling stories for children(P_interaction=0.017,0.041,0.017).The significant association between rs3779031 and the risk of dyslexia?OR=2.649,95%CI=1.307–5.369?was found in children whose mother do non-manual jobs.As to paternal education level,only in junior college or above group,the significant association between rs3779031 and dyslexia?OR=2.52,95%CI=1.291–4.916?was observed.With respect to home literacy environment,the influence of rs3779031 on the risk of dyslexia was significant in children whose parents telling stories more frequently?OR=1.714,95%CI=1.194–2.462?.After FDR adjustment for multiple comparisons,the P values of the interactions were greater than 0.05.Conclusion:There may be a bioecological interaction between CNTNAP2rs3779031 and home environment factors including maternal occupation,paternal education level,and parents telling stories for children.