Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18

Scerri, Thomas; Paracchini, Silvia; Morris, Andrew P.; MacPhie, I. Laurence; Talcott, Joel B.; Stein, John; Smith, Shelley D.; Pennington, Bruce F.; Olson, Richard K.; DeFries, John C.; Monaco, Anthony P.

doi:10.1371/journal.pone.0013712

Cited by 38 publications

(41 citation statements)

References 65 publications

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“…The samples from cohorts 1 and 2 were selected as part of an ongoing study of dyslexia [43], [44]. The samples from cohorts 3 and 4 are part of the Avon Longitudinal Study of Parents and Children (ALSPAC).…”

Section: Resultsmentioning

confidence: 99%

Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

et al. 2013

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Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10−9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development.

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Section: Resultsmentioning

confidence: 99%

Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

et al. 2013

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“…Two more recent studies have identified new candidate genes for dyslexia, both on chromosome 18 (MC5R, DYM, and NEDD4L) 118 and one shared with LI (CMIP), 119 but these results need to be replicated.…”

Section: Etiologymentioning

confidence: 99%

Developmental dyslexia

Peterson¹,

Pennington²

2012

The Lancet

618

445

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Summary Dyslexia is a neurodevelopmental disorder that is characterized by slow and inaccurate word recognition. Dyslexia has been found in every culture studied, and mounting evidence underscores cross-linguistic similarity in its neurobiological and neurocognitive bases. There has been considerable progress across levels of analysis in the last five years. At a neuropsychological level, the phonological theory remains the most compelling, though it is increasingly clear that phonological problems interact with other cognitive risk factors. At a neurobiological level, recent research confirms that dyslexia is characterized by dysfunction of the normal left hemisphere language network and also implicates abnormal white matter development. Studies accounting for reading experience demonstrate that many observed neural differences reflect causes rather than effects of dyslexia. At an etiologic risk level, six candidate genes have been identified, and there is evidence for gene by environment interaction. This review includes a focus on these and other recent developments.

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“…Scerri et al (2010) conducted linkage analyses on 264 families in the UK and 155 families in the U.S., each with at least one child with dyslexia. Lind, Luciano, Wright, Montgomery, Martin, and Bates (2010) performed linkage and association studies on the reading and spelling abilities of adolescent twins in 522 families not selected on basis of reading disability.…”

Section: Understanding and Defining Dyslexiamentioning

confidence: 99%

Evidence-Based Reading and Writing Assessment for Dyslexia in Adolescents and Young Adults

Nielsen

Abbott

Griffin

et al. 2016

LDMJ

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The same working memory and reading and writing achievement phenotypes (behavioral markers of genetic variants) validated in prior research with younger children and older adults in a multi-generational family genetics study of dyslexia were used to study 81 adolescent and young adults (ages 16 to 25) from that study. Dyslexia is impaired word reading and spelling skills below the population mean and ability to use oral language to express thinking. These working memory predictor measures were given and used to predict reading and writing achievement: Coding (storing and processing) heard and spoken words (phonological coding), read and written words (orthographic coding), base words and affixes (morphological coding), and accumulating words over time (syntax coding); Cross-Code Integration (phonological loop for linking phonological name and orthographic letter codes and orthographic loop for linking orthographic letter codes and finger sequencing codes), and Supervisory Attention (focused and switching attention and self-monitoring during written word finding). Multiple regressions showed that most predictors explained individual difference in at least one reading or writing outcome, but which predictors explained unique variance beyond shared variance depended on outcome. ANOVAs confirmed that research-supported criteria for dyslexia validated for younger children and their parents could be used to diagnose which adolescents and young adults did (n=31) or did not (n=50) meet research criteria for dyslexia. Findings are discussed in reference to the heterogeneity of phenotypes (behavioral markers of genetic variables) and their application to assessment for accommodations and ongoing instruction for adolescents and young adults with dyslexia.

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Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18

Cited by 38 publications

References 65 publications

Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

Developmental dyslexia

Evidence-Based Reading and Writing Assessment for Dyslexia in Adolescents and Young Adults

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