Association analysis of dyslexia candidate genes in a Dutch longitudinal sample

Eur J Hum Genet. 2017 Apr;25(4):452-460. doi: 10.1038/ejhg.2016.194. Epub 2017 Jan 11.

Abstract

Dyslexia is a common specific learning disability with a substantive genetic component. Several candidate genes have been proposed to be implicated in dyslexia susceptibility, such as DYX1C1, ROBO1, KIAA0319, and DCDC2. Associations with variants in these genes have also been reported with a variety of psychometric measures tapping into the underlying processes that might be impaired in dyslexic people. In this study, we first conducted a literature review to select single nucleotide polymorphisms (SNPs) in dyslexia candidate genes that had been repeatedly implicated across studies. We then assessed the SNPs for association in the richly phenotyped longitudinal data set from the Dutch Dyslexia Program. We tested for association with several quantitative traits, including word and nonword reading fluency, rapid naming, phoneme deletion, and nonword repetition. In this, we took advantage of the longitudinal nature of the sample to examine if associations were stable across four educational time-points (from 7 to 12 years). Two SNPs in the KIAA0319 gene were nominally associated with rapid naming, and these associations were stable across different ages. Genetic association analysis with complex cognitive traits can be enriched through the use of longitudinal information on trait development.

MeSH terms

  • Child
  • Child Development
  • Cytoskeletal Proteins
  • Dyslexia / genetics*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Microtubule-Associated Proteins / genetics
  • Nerve Tissue Proteins / genetics*
  • Netherlands
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Immunologic / genetics
  • Roundabout Proteins

Substances

  • Cytoskeletal Proteins
  • DCDC2 protein, human
  • DNAAF4 protein, human
  • KIAA0319 protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptors, Immunologic