Association of Attention-Deficit/Hyperactivity Disorder with a Candidate Region for Reading Disabilities on Chromosome 6p

Couto, Jillian M.; Gomez, Lissette; Wigg, Karen; Ickowicz, Abel; Pathare, Tejaswee; Malone, Molly; Kennedy, James L.; Schachar, Russell; Barr, Cathy L.

doi:10.1016/j.biopsych.2009.02.016

Cited by 49 publications

(46 citation statements)

References 57 publications

(132 reference statements)

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“…Replication of this SNP, along with expression and/or sequencing analyses to uncover its associated functional effects, would be desirable. We did not find significant support for association of reading and spelling with rs793862, the most widely genotyped polymorphism in DCDC2 association studies; though we did observe the same at-risk allele as in earlier studies 10,11,36,37 (the T-allele conferred a reading disadvantage of just 0.02 SD). Contradictory findings have been reported for this SNP: from nominally significant associations, 8,9 to associations specific only in the most severely affected families, 10 to the reverse effect (a nominally significant association in independent UK samples that disappeared when the sample was restricted to individuals with severe spelling difficulties 7 ), to no support for association of rs793862 to dyslexia in a cohort of US families.…”

Section: Discussioncontrasting

confidence: 51%

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

et al. 2010

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The 6p21-p22 chromosomal region has been identified as a developmental dyslexia locus both in linkage and association studies, the latter generating evidence for the doublecortin domain containing 2 (DCDC2) as a candidate gene at this locus (and also for KIAA0319). Here, we report an association between DCDC2 and reading and spelling ability in 522 families of adolescent twins unselected for reading impairment. Family-based association was conducted on 21 single nucleotide polymorphisms (SNPs) in DCDC2 using quantitative measures of lexical processing (irregular-word reading), phonological decoding (non-word reading) and spelling-based measures of dyslexia derived from the Components of Reading Examination test. Significant support for association was found for rs1419228 with regular-word reading and spelling (P¼0.002) as well as irregular-word reading (P¼0.004), whereas rs1091047 was significantly associated (P¼0.003) with irregular-word reading (a measure of lexical storage). Four additional SNPs (rs9467075, rs9467076, rs7765678 and rs6922023) were nominally associated with reading and spelling. This study provides support for DCDC2 as a risk gene for reading disorder, and suggests that this risk factor acts on normally varying reading skill in the general population.

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Section: Discussioncontrasting

confidence: 51%

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

et al. 2010

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“…Both rs793862 and rs807701, and their haplotype, have also been tested in a sample of families with ADHD probands and also tested for reading measures, and revealed association with attentional phenotypes, but not the reading phenotypes. Although the association of rs793862 to DD or ADHD in four of the five studies appears to be with the minor allele [35,40,121,158], in the remaining British sample, it is with the major allele [80]. However, the association observed in this British sample is modest (P values from 0.02 to 0.04), suggesting it may be a type I error.…”

Section: Dyx2 On Chromosomementioning

confidence: 66%

Genetics of developmental dyslexia

Scerri

Schulte‐Körne

2009

Eur Child Adolesc Psychiatry

191

137

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Developmental dyslexia is a highly heritable disorder with a prevalence of at least 5% in school-aged children. Linkage studies have identified numerous loci throughout the genome that are likely to harbour candidate dyslexia susceptibility genes. Association studies and the refinement of chromosomal translocation break points in individuals with dyslexia have resulted in the discovery of candidate genes at some of these loci. A key function of many of these genes is their involvement in neuronal migration. This complements anatomical abnormalities discovered in dyslexic brains, such as ectopias, that may be the result of irregular neuronal migration.

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“…Most of the genetic associations with dyslexia cluster around the 5' end of the KIAA0319 gene and generally show the same allelic trends across independent studies (Francks et al, 2004, Cope et al, 2005Schumacher et al, 2007;Luciano et al, 2007;Paracchini et al, 2008;Couto et al, 2009;Dennis et al, 2009;Wilcke et al, 2009). Francks et al (2004) identified 1 main RD risk haplotype comprising 3 SNPs (rs4504469, rs2038137, and rs2143340) with a frequency of 12% in families from the United Kingdom and the United States.…”

Section: Introductionmentioning

confidence: 73%

Study of candidate genes for dyslexia in Brazilian individuals

Svidnicki¹,

Salgado²,

Lima³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Dyslexia or reading disability (RD) is the most common childhood learning disorder and a significantly heritable trait. Many recent studies have investigated the genetic basis of dyslexia, and several candidate genes have been proposed. Among these, DCDC2 and KIAA0319 have emerged as the strongest candidate genes for dyslexia; however studies have not provided uniformly supportive results. The aim of this study was to assess the contribution of proposed candidate genes to the molecular etiology of dyslexia in a Brazilian sample. Large deletions and duplications in the candidate genes DCDC2, KIAA0319, and ROBO1 were investigated in 51 dyslexic subjects. Furthermore, a family-based association study was performed to investigate whether associations observed in other populations with variants in the Dyslexia candidate genes DCDC2 and KIAA0319 genes were reproducible in Brazilian dyslexic individuals. Our analysis did not detect any deletions or duplications in the genes studied, and we found no evidence that the allelic variants in the two candidate genes were significantly associated with RD in our sample. Our data do not support a role of the DCDC2/KIAA0319 locus in influencing dyslexia as a categorical trait. Given the genetic complexity of dyslexia, it is plausible that both genes contribute to an increased risk, but the relative influence of these 2 genes on RD varies in different study samples, and/or depends on analytical approaches.

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Association of Attention-Deficit/Hyperactivity Disorder with a Candidate Region for Reading Disabilities on Chromosome 6p

Abstract: Overall this study supports a previous linkage study of ADHD indicating a risk gene for ADHD on 6p and points to VMP or DCDC2 as the most likely candidates.

Cited by 49 publications

References 57 publications

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

Genetics of developmental dyslexia

Study of candidate genes for dyslexia in Brazilian individuals

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