Genetic variant in<i>KIAA0319</i>, but not in<i>DYX1C1</i>, is associated with risk of dyslexia: An integrated meta‐analysis

Zou, Li; Chen, Wei; Shao, Shuai; Sun, Ziyong; Zhong, Rong; Shi, Junxin; Miao, Xiaoping; Song, Ranran

doi:10.1002/ajmg.b.32102

Cited by 38 publications

(34 citation statements)

References 46 publications

(62 reference statements)

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“…Meanwhile, another study focusing on a 575-kb region of chromosome 6p22.2 also reported significant association of KIAA0319 with DD by identifying rs4504469 as well as a two-marker haplotype rs4504469-rs6935076 [Cope et al, 2005]. The association of KIAA0319 with DD was also supported by association studies in the UK [Harold et al, 2006], Canadian [Elbert et al, 2011] and Indian populations [Venkatesh et al, 2013] as well as a recent meta-analysis [Zou et al 2012]. In general populations unselected for DD, KIAA0319 was found to be associated with reading abilities as well [Luciano et al, 2007;Paracchini et al, 2008;Scerri et al, 2011].…”

Section: Introduction Neuropsychiatric Geneticsmentioning

confidence: 81%

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Sun

Gao

Zhou

et al. 2014

American J of Med Genetics Pt B

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Developmental dyslexia (DD) is characterized by difficulties in reading and spelling independent of intelligence, educational backgrounds and neurological injuries. Increasing evidences supported DD as a complex genetic disorder and identified four DD candidate genes namely DYX1C1, DCDC2, KIAA0319 and ROBO1. As such, DCDC2 and KIAA0319 are located in DYX2, one of the most studied DD susceptibility loci. However, association of these two genes with DD was inconclusive across different populations. Given the linguistic and genetic differences between Chinese and other populations, it is worthwhile to investigate association of DCDC2 and KIAA0319 with Chinese dyslexic children. Here, we selected 60 tag SNPs covering DCDC2 and KIAA0319 followed by high density genotyping in a large unrelated Chinese cohort with 502 dyslexic cases and 522 healthy controls. Several SNPs (P min ¼ 0.0192) of DCDC2 and KIAA0319 as well as a four-maker haplotype (P adjusted ¼ 0.0289, Odds Ratio (OR) ¼ 1.3400) of KIAA0319 showed nominal association with DD. However, none of these results survived Bonferroni correction for multiple comparisons. Thus, the association of DCDC2 and KIAA0319 with DD in Chinese population should be further validated and their contribution to DD etiology and pathology should be interpreted with caution.

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Section: Introduction Neuropsychiatric Geneticsmentioning

confidence: 81%

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Sun

Gao

Zhou

et al. 2014

American J of Med Genetics Pt B

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“…Importantly, a recent meta-analysis that integrated case-control and transmission/disequilibrium test studies supported the role of this gene in the risk of dyslexia (Zou et al, 2012). Recent work with rats (who have almost identical speech discrimination thresholds to humans) whose expression of the homolog of the human gene KIAA0319 was reduced (by in utero RNAi transfection of Kiaa0319 ) displayed much variability in neural excitability, neural discriminability and latency to speech sounds, findings which offer a putative mechanism for how this so-called dyslexia gene may impair phoneme processing namely by altering auditory cortical responses (Centanni et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

Category fluency, latent semantic analysis and schizophrenia: a candidate gene approach

Nicodemus

Elvevåg

Foltz

et al. 2014

Cortex

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Background Category fluency is a widely used task that relies on multiple neurocognitive processes and is a sensitive assay of cortical dysfunction, including in schizophrenia. The test requires naming of as many words belonging to a certain category (e.g., animals) as possible within a short period of time. The core metrics are the overall number of words produced and the number of errors, namely non-members generated for a target category. We combine a computational linguistic approach with a candidate gene approach to examine the genetic architecture of this traditional fluency measure. Methods In addition to the standard metric of overall word count, we applied a computational approach to semantics, Latent Semantic Analysis (LSA), to analyse the clustering pattern of the categories generated, as it likely reflects the search in memory for meanings. Also, since fluency performance probably also recruits verbal learning and recall processes, we included two standard measures of this cognitive process: the Wechsler Memory Scale and California Verbal Learning Test. To explore the genetic architecture of traditional and LSA-derived fluency measures we employed a candidate gene approach focused on SNPs with known function that were available from a recent genome-wide association study (GWAS) of schizophrenia. The selected candidate genes were associated with language and speech, verbal learning and recall processes, and processing speed. A total of 39 coding SNPs were included for analysis in 665 subjects. Results and Discussion Given the modest sample size, the results should be regarded as exploratory and preliminary. Nevertheless, the data clearly illustrate how extracting the meaning from participants’ responses, by analysing the actual content of words, generates useful and neurocognitively viable metrics. We discuss three replicated SNPs in the genes ZNF804A, DISC1 and KIAA0319, as well as the potential for computational analyses of linguistic and textual data in other genomics tasks.

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“…1) (Cardon et al 1994; Deffenbacher et al 2004; Gayán et al 1999; Kaplan et al 2002). Two DYX2 genes, DCDC2 and KIAA0319 , have been identified as RD risk genes, with considerable genetic and functional molecular evidence supporting the involvement of each (Couto et al 2010; Cope et al 2005; Elbert et al 2011; Francks et al 2004; Harold et al 2006; Lind et al 2010; Luciano et al 2007; Marino et al 2012; Meng et al 2005; Newbury et al 2011; Paracchini et al 2006, 2008; Powers et al 2013; Scerri et al 2011; Schumacher et al 2006; Wilcke et al 2009; Zhong et al 2013; Zou et al 2012). Both DCDC2 and KIAA0319 function in neuronal migration during brain development, as demonstrated by in utero RNAi knockdown studies in rat (Meng et al 2005; Paracchini et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ

et al. 2014

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Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI—and their associated deficits—are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-014-1427-3) contains supplementary material, which is available to authorized users.

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Genetic variant inKIAA0319, but not inDYX1C1, is associated with risk of dyslexia: An integrated meta‐analysis

Cited by 38 publications

References 46 publications

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Category fluency, latent semantic analysis and schizophrenia: a candidate gene approach

Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ

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