Dataset Information

Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population.

ABSTRACT: KIAA0319 at the DYX2 locus is one of the most extensively studied candidate genes for developmental dyslexia (DD) owing to its important role in neuronal migration. Previous research on associations between KIAA0319 genetic variations and DD has yielded inconsistent results. It is important to establish a more precise estimate of the DD risk associated with these genetic variations. We carried out a meta-analysis of association studies involving KIAA0319 polymorphisms and DD risk. The results of pooled analysis indicated that none of the six investigated markers in or near the KIAA0319 gene are associated with DD. However, a stratified analysis by the study population revealed opposite associations involving KIAA0319 rs4504469 in European and Asian subgroups. The stratified analysis also showed that the KIAA0319 rs9461045 minor allele (T allele) has a protective effect in Asians. This meta-analysis has allowed us to establish the effects of specific KIAA0319 polymorphisms on DD risk with greater precision, as they vary across populations; analyzing one single nucleotide polymorphism at a time could not fully explain the genetic association for DD.

SUBMITTER: Shao S

PROVIDER: S-EPMC4964335 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population.

Shao Shanshan S Niu Yanfeng Y Zhang Xiaohui X Kong Rui R Wang Jia J Liu Lingfei L Luo Xiu X Zhang Jiajia J Song Ranran R

Scientific reports 20160728

KIAA0319 at the DYX2 locus is one of the most extensively studied candidate genes for developmental dyslexia (DD) owing to its important role in neuronal migration. Previous research on associations between KIAA0319 genetic variations and DD has yielded inconsistent results. It is important to establish a more precise estimate of the DD risk associated with these genetic variations. We carried out a meta-analysis of association studies involving KIAA0319 polymorphisms and DD risk. The results of ...[more]

PMID: 27464509

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Project description:Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading.

Project description:Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8-12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms (rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266) in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models (Codominant, Dominant, Recessive, Heterozygote advantage, and Allele) between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs (rs807724, rs2274305, and rs4599626) were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype (rs9295619-rs807701-rs807724-rs2274305) and the T-A of the two-marker haplotype (rs3765502-1087266) were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Dataset Information

Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population.

Publications

Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population.

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