Further evidence for DYX1C1 as a susceptibility factor for dyslexia

Dahdouh, Faten; Anthoni, Heidi; Tapia-Páez, Isabel; Peyrard-Janvid, Myriam; Schulte‐Körne, Gerd; Warnke, Andreas; Remschmidt, Helmut; Ziegler, Andreas; Kere, Juha; Müller‐Myhsok, Bertram; Nöthen, Markus M.; Schumacher, Johannes; Zucchelli, Marco

doi:10.1097/ypg.0b013e32832080e1

Cited by 63 publications

(65 citation statements)

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“…The results did not support association for the two SNPs reported as associated with dyslexia in Finnish readers. 1 These findings are consistent both with other data, suggesting that the association of markers rs3743205 and rs61761345 identified by Taipale et al may be specific to the Finnish genetic background 4 and with other data suggesting that DYX1C1 is nevertheless associated with reading disability in non-Finnish populations, 28,31 as well as with short-term memory. 28,30 Overall, these data significantly increase support for a role of DYX1C1 in dyslexia and, perhaps separately, in short-term storage of verbal information.…”

Section: Discussionsupporting

confidence: 81%

“…1 These findings are consistent both with other data, suggesting that the association of markers rs3743205 and rs61761345 identified by Taipale et al may be specific to the Finnish genetic background 4 and with other data suggesting that DYX1C1 is nevertheless associated with reading disability in non-Finnish populations, 28,31 as well as with short-term memory. 28,30 Overall, these data significantly increase support for a role of DYX1C1 in dyslexia and, perhaps separately, in short-term storage of verbal information. 30 These data suggest a new candidate for a functional mutation in DYX1C1; given the known role of DYX1C1 in neuronal migration, 17,18 the results bolster the early observation of Galaburda et al 55 that dyslexia may be associated with molecular layer ectopia and microgyria.…”

Section: Discussionsupporting

confidence: 81%

“…Wigg et al also reported significant association for rs11629841 and for haplotypes involving this SNP (rs11629841/rs3743204 and rs11629841/rs692691) as well as for the rs3743205/rs61761345 haplotype reported by Taipale. Dahdouh et al 28 examined the two markers (rs3743205 and rs61761345) reported by Taipale et al and additional SNPs in the promoter (rs12899331, rs16787 and rs8043269 (the latter dropped at assay assessment)) and the coding region (rs3743204 and rs600753), a total of 8 SNPs in 366 family trios ascertained based on a X1 s.d. spellingability discrepancy from that predicted from intelligence test scores (IQ).…”

Section: Introductionmentioning

confidence: 99%

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Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Bates

Lind²,

Luciano

et al. 2009

Mol Psychiatry

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The status of DYX1C1 (C15q21.3) as a susceptibility gene for dyslexia is unclear. We report the association of this gene with reading and spelling ability in a sample of adolescent twins and their siblings. Family-based association analyses were carried out on 13 single-nucleotide polymorphisms (SNPs) in DYX1C1, typed in 790 families with up to 5 offspring and tested on 6 validated measures of lexical processing (irregular word) and grapheme-phoneme decoding (pseudo-word) reading-and spelling-based measures of dyslexia, as well as a short-term memory measure. Significant association was observed at the misssense mutation rs17819126 for all reading measures and for spelling of lexical processing words, and at rs3743204 for both irregular and nonword reading. Verbal short-term memory was associated with rs685935. Support for association was not found at rs3743205 and rs61761345 as previously reported by Taipale et al., but these SNPs had very low (0.002 for rs3743205) minor allele frequencies in this sample. These results suggest that DYX1C1 influences reading and spelling ability with additional effects on short-term information storage or rehearsal. Missense mutation rs17819126 is a potential functional basis for the association of DYX1C1 with dyslexia.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Bates

Lind²,

Luciano

et al. 2009

Mol Psychiatry

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“…The markers rs600753 and rs16787 were previously found to be significant in several combinations of haplotypes [Dahdouh et al, 2009]. The rs1789126 marker was selected because of a positive association in an Australian sample [Bates et al, 2010], and the rs1289331 was selected as it was suggested to be the binding site of the SP1 transcription factor [Tapia-Paez et al, 2008].…”

Section: Family-based Association Analysismentioning

confidence: 99%

A family‐based association analysis and meta‐analysis of the reading disabilities candidate gene DYX1C1

Tran

Gagnon

Wigg

et al. 2013

American J of Med Genetics Pt B

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Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the À3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the À3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and À3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between À3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (À3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the À3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs À3G/A and 1249G/T and RD. Ó 2013 Wiley Periodicals, Inc.Key words: dyslexia; chromosome 15q; EKN1; genetics INTRODUCTIONSpecific reading disabilities (RD), or developmental dyslexia, refer to an unexpected and specific difficulty in learning to read despite normal or above average intelligence, education, and socioeconomic opportunity. RD is likely caused by a dysfunction of neural systems involved in cognitive skills required for reading [Habib, 2000]. A core deficit observed in dyslexics involves the processing of phonemes, the most basic unit of speech sounds, which persist into adulthood [Bruck, 1992;Shaywitz et al., 1999;Ramus et al., 2003]. Individuals with RD have difficulty segmenting words into their phonological elements, impairing their ability in learning to read. Several other reading components have been shown to be impaired in individuals with RD including orthographic coding, single-word reading, rapid automatic naming, and spelling [Denckla and Rudel, 1976;Paulesu et al., 2001;Francks et al., 2002]. With an estimated Additional supporting information may be found in the online version of this article. 146Neuropsychiatric Genetics prevalence ranging from 5% to 17.5% in school-aged children, RD is the most common learning disability and affects four out of five individuals with learning disabilities [Shaywitz et al., 1990;Shaywitz, 1998;Katusic et al., 2001]. There is substantial evidence to suggest that RD is both familial and heritable. RD has bee...

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“…DYX1C1 has also been associated with reading and spelling ability in a large unselected group of adolescents from Australia. 15 Furthermore, it has been shown that dyslexia-associated variants within the promoter region of DYX1C1 16 influence the binding affinity of transcription factor complexes. 17 Two genes have been reported to be associated with dyslexia within the linkage region on chromosome 6p22.2: DCDC2 (doublecortin domain-containing protein 2, MIM 605755) [18][19][20] and KIAA0319 (MIM 609269).…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort

et al. 2013

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Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children -the NeuroDys cohort -that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

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Further evidence for DYX1C1 as a susceptibility factor for dyslexia

Abstract: As significant association was proved in our sample, we could also conclude that denser maps, sex information, and well-defined subphenotypes are crucial to correctly determine the contribution of DYX1C1 to dyslexia.

Cited by 63 publications

References 23 publications

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

A family‐based association analysis and meta‐analysis of the reading disabilities candidate gene DYX1C1

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort

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