本文選題：漢語閱讀障礙　切入點(diǎn)：社會(huì)經(jīng)濟(jì)地位　出處：《華中科技大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：本研究擬從流行病學(xué)特點(diǎn)、遺傳因素以及環(huán)境與遺傳的交互作用三個(gè)層次逐步探討漢語閱讀障礙的影響因素,為漢語閱讀障礙的預(yù)防、診斷和干預(yù)提供理論依據(jù)。第一部分 湖北省四市/縣漢語閱讀障礙兒童的流行病學(xué)調(diào)查及影響因素分析目的：了解湖北省漢語閱讀障礙兒童的檢出率及其分布特征,探索漢語閱讀障礙的流行病學(xué)特點(diǎn)及影響因素。方法：采取整群抽樣的方法,抽取湖北省四個(gè)市/縣共46所小學(xué)的3-6年級(jí)全體學(xué)生為研究對(duì)象,進(jìn)行問卷調(diào)查。共發(fā)放問卷25,150份,收回有效問卷19,844份。采用χ2檢驗(yàn)和趨勢(shì)檢驗(yàn)進(jìn)行數(shù)據(jù)分析。結(jié)果：漢語閱讀障礙兒童的總檢出率為3.6%,男生顯著高于女生(χ2=254.02,P0.001)；χ2檢驗(yàn)的結(jié)果顯示,漢語閱讀障礙兒童在反映社會(huì)經(jīng)濟(jì)地位的變量上(包括家庭成員平均月收入、父親文化程度、母親文化程度)和反映家庭閱讀環(huán)境的變量上(包括兒童是否參加課外活動(dòng)如閱讀,兒童的自主學(xué)習(xí)習(xí)慣,兒童是否有固定閱讀時(shí)間,父母閱讀書籍的頻率,父母給孩子購買書籍的間隔期,父母每年給孩子買書的花銷,父母給孩子講故事的頻率,父母鼓勵(lì)孩子看課外書籍的頻率,父母買孩子喜歡書的頻率)的分布差異均有顯著性意義(χ2檢驗(yàn)的P值均小于0.05)。趨勢(shì)檢驗(yàn)的結(jié)果進(jìn)一步提示,社會(huì)經(jīng)濟(jì)地位越好,家庭閱讀環(huán)境越好,兒童閱讀障礙的檢出率越低(趨勢(shì)檢驗(yàn)的P值均小于0.001)。結(jié)論：性別、家庭社會(huì)經(jīng)濟(jì)地位和家庭閱讀環(huán)境是漢語閱讀障礙發(fā)生的影響因素。第二部分神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)基因變異與漢語閱讀障礙易感性的關(guān)聯(lián)研究目的：探討神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)上的基因變異與漢語閱讀障礙易感性的關(guān)系,尋找影響漢語閱讀障礙發(fā)生的遺傳因素。方法：采用病例-對(duì)照的研究方法,從409名漢語閱讀障礙組兒童和410名對(duì)照組兒童的口腔拭子中提取DNA,對(duì)神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)中的6個(gè)關(guān)鍵基因(DYX1C1、DCDC2、K1AA0319、ROBO1、KIAA0319L和DOCK4)上的16個(gè)功能性常見變異進(jìn)行基因分型,采用非條件logistic回歸法、決策樹分析法、累計(jì)效應(yīng)分析法進(jìn)行統(tǒng)計(jì)分析。結(jié)果：①單因素logistic回歸法的結(jié)果顯示,經(jīng)錯(cuò)誤發(fā)現(xiàn)率(False discovery rate, FDR)校正后,KIAA0319L rs28366021 G到A的突變顯著降低了漢語閱讀障礙的患病風(fēng)險(xiǎn)(OR=0.67,95% CI=0.51-0.89),K1AA0319 rs4504469C到T的突變和DOCK4 rs2074130 C到T的突變均顯著增加了漢語閱讀障礙的患病風(fēng)險(xiǎn)(OR=1.61,95% CI=1.17-2.20；OR=1.68,95% CI=1.20-2.35);②經(jīng)決策樹預(yù)測(cè),DOCK4 rs2074130、KIAA0319 rs4504469、DCDC2rs2274305和KIAA0319L rs28366021之間可能存在交互作用；與危險(xiǎn)性最低組(同時(shí)攜帶rs2074130 CC、rs4504469 CC和rs2274305 GG基因型)相比,同時(shí)攜帶rs2074130 CC、rs4504469 CT或TT和rs28366021 GG基因型的個(gè)體漢語閱讀障礙的患病風(fēng)險(xiǎn)顯著增加(OR=2.29,95% CI=1.39-3.77),而同時(shí)攜帶rs2074130 CT或TT和rs28366021 GG基因型的個(gè)體漢語閱讀障礙的患病風(fēng)險(xiǎn)最高(OR=2.98,95% CI=1.87-4.75)：③對(duì)DOCK4 rs2074130、K1AA0319 rs4504469、DCDC2 rs2274305和K1AA0319L rs28366021的累計(jì)效應(yīng)分析顯示,與攜帶0-2個(gè)危險(xiǎn)等位基因組相比,攜帶3-4個(gè)危險(xiǎn)等位基因組和攜帶5-7個(gè)危險(xiǎn)等位基因組均顯著增加了漢語閱讀障礙的患病風(fēng)險(xiǎn)(OR=1.60,95% CI=1.19-2.15；OR=2.74,95% CI=1.42-5.32)；趨勢(shì)檢驗(yàn)亦有統(tǒng)計(jì)學(xué)意義(P0.001)。結(jié)論:神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)上的KIAA0319L rs28366021、KIAA0319rs4504469或DOCK4 rs2074130單位點(diǎn)變異與漢語閱讀障礙的發(fā)病風(fēng)險(xiǎn)顯著相關(guān),DOCK4 rs2074130、KIAA0319 rs4504469、DCDC2 rs2274305和KIAA0319Lrs28366021多位點(diǎn)的交互作用和累積效應(yīng)可能對(duì)漢語閱讀障礙的發(fā)病風(fēng)險(xiǎn)產(chǎn)生更為顯著的影響。第三部分家庭社會(huì)經(jīng)濟(jì)地位和家庭閱讀環(huán)境與神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)基因的交互作用在漢語閱讀障礙發(fā)生中的初步探討目的：在前兩部分的基礎(chǔ)上,進(jìn)一步探討影響漢語閱讀障礙發(fā)生的環(huán)境與基因的交互作用。方法：采用病例-對(duì)照的研究設(shè)計(jì)和logistic回歸法,分析家庭社會(huì)經(jīng)濟(jì)地位和家庭閱讀環(huán)境與神經(jīng)元遷移調(diào)控網(wǎng)絡(luò)上的易感基因變異在漢語閱讀障礙上的兩兩交互作用。結(jié)果：FDR校正前,在漢語閱讀障礙的危險(xiǎn)性上,父母文化程度與KIAA0319L rs28366021位點(diǎn)的基因型存在顯著的交互作用(Pinteraction= 0.048),父母閱讀書籍的頻率與KIAA0319L rs28366021位點(diǎn)的基因型存在顯著的交互作用(Pinteraction=0.023),且交互作用的模型均符合生物生態(tài)學(xué)模型。經(jīng)FDR校正后,以上兩個(gè)交互作用的P值均大于0.05。結(jié)論：在漢語閱讀障礙的發(fā)生中,KIAA0319L rs28366021與父母文化程度和父母閱讀書籍的頻率之間可能存在交互作用,交互模型為生物生態(tài)學(xué)模型。但考慮到多重檢驗(yàn)可能帶來的假陽性,以上結(jié)果有待更大樣本的驗(yàn)證。
[Abstract]:This paper from the epidemiological features, influencing factors of three levels of interaction of genetic factors and environmental and genetic probes into Chinese dyslexia, for the prevention of Chinese dyslexia, provide a theoretical basis for the diagnosis and intervention. The first part of the Hubei Province four City / county Chinese reading factors epidemiological investigation and analysis of influence of disorder in children Objective: to understand the Hubei Province Chinese dyslexic children the prevalence and distribution characteristics, epidemiological characteristics and related factors of Chinese dyslexia. Methods: by cluster sampling method, extraction of four cities in Hubei province / all the county a total of 46 primary school students of Grade 3-6 as the research object, carries on the questionnaire survey. A total of 25150 questionnaires. 19844 copies of valid questionnaires. Using the chi square test 2 test and trend data analysis. Results: Chinese dyslexic children total detection rate was 3.6%, the boys show The higher than girls (x 2=254.02, P0.001 x 2); the results showed that Chinese dyslexic children in reflecting the social economic status variables (including the average family income, father's education, mother's education level) and reflect the family reading environment variables (including children whether to participate in extracurricular activities such as reading, children independent learning habits, whether children have a fixed reading time, reading books, parents frequency, parents give their children buy books every year interval, parents give their children to buy books spending, parents give children to tell the story of the frequency, parents encourage their children to read the extracurricular books frequency, parents buy children love the book) has frequency distribution the difference was significant (x2 test of 2 P values were less than 0.05). Trend test results further suggest that the social economic status of family reading environment better, better, the detection rate of dyslexia in children The lower (trend test P values were less than 0.001). Conclusion: gender, family and social economic status of the family reading environment are risk factors of Chinese dyslexia. The second part of the neuronal migration Association of genetic regulatory networks to gene mutation and Chinese dyslexia: To investigate the relationship between neuronal migration gene mutation and Chinese dyslexia susceptibility regulation on the network, looking for genetic factors disorder of Chinese reading effect. Methods: a case-control study, DNA from disorder group children and 410 children in control group oral swabs from 409 Chinese reading, 6 key of neuronal migration in gene regulatory networks (DYX1C1, DCDC2, K1AA0319 ROBO1, KIAA0319L, and DOCK4) on the 16 functional common variants were genotyped using non conditional logistic regression, decision tree analysis, the cumulative effect analysis method Statistical analysis was performed. Results: the single factor Logistic regression analysis showed that the false discovery rate (False discovery rate FDR KIAA0319L rs28366021 G) after correction to A mutation significantly reduces the risk of dyslexia (OR=0.67,95% CI=0.51-0.89), the prevalence of K1AA0319 rs4504469C to T rs2074130 C mutation and DOCK4 to T the mutation significantly increased the risk of dyslexia in (OR=1.61,95% CI=1.17-2.20 OR=1.68,95%; CI=1.20-2.35); the decision tree prediction, DOCK4 rs2074130, KIAA0319 rs4504469, the possible interaction between DCDC2rs2274305 and KIAA0319L rs28366021; and the lowest risk group (rs2074130 CC rs4504469 CC with rs2274305, and GG genotype) compared with rs2074130 CC, a significant increase in the risk of individual Chinese rs4504469 CT or TT and rs28366021 disorder GG genotype prevalence (O reading R=2.29,95% CI=1.39-3.77), and the individual Chinese obstacles while carrying rs2074130 or TT CT and rs28366021 GG genotypes in reading the risk highest (OR=2.98,95% CI=1.87-4.75): the DOCK4 rs2074130, K1AA0319 rs4504469, DCDC2 rs2274305 and K1AA0319L rs28366021 cumulative effect analysis showed that compared with the 0-2 risk alleles, carrying 3-4 risk etc. a genome and carrying 5-7 risk allele significantly increased the risk of dyslexia (OR=1.60,95% CI=1.19-2.15; OR=2.74,95% CI=1.42-5.32 disease); trend test was also statistically significant (P0.001). Conclusion: the regulation of neuronal migration on the network KIAA0319L rs28366021, was significantly related to the risk of KIAA0319rs4504469 or DOCK4 rs2074130 point mutation and Chinese DOCK4 rs2074130 KIAA0319 dyslexia, rs4504469, DCDC2 rs2274305 and KIAA0319L The interaction of rs28366021 is more and the cumulative effect of risk of Chinese dyslexia has a more significant effect. The interaction of the third part of the family socioeconomic status and family reading environment and gene regulatory networks of neuronal migration disorders in the preliminary study in Chinese Reading: on the basis of the two parts, further study the interaction of environmental and genetic disorders of the Chinese reading effect. Methods: the study design and logistic regression method using case-control analysis, family socioeconomic status and family reading environment and regulation of neuronal migration network susceptible gene mutation in 22 interaction barriers on Chinese reading. Results: FDR before correction, in the risk of Chinese dyslexia, there was significant interaction between genotype KIAA0319L and parents'education locus rs28366021 ( Pinteraction= 0.048), there was significant interaction between genotype frequency and rs28366021 locus KIAA0319L parents read the books (Pinteraction=0.023), and the interaction model are consistent with the bio ecological model. After FDR correction, the above two interaction P values were greater than 0.05.. Conclusion: in the event of Chinese dyslexia, there may be the interaction between KIAA0319L rs28366021 and the cultural degree of parents and parents reading frequency, interaction model for biological ecology model. But considering multiple testing may bring false positive, the above results are to be confirmed with larger samples.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.94

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