Imaging genetics of FOXP2 in dyslexia

Abstract

Dyslexia is a developmental disorder characterised by extensive difficulties in the acquisition of reading or spelling. Genetic influence is estimated at 50-70%. However, the link between genetic variants and phenotypic deficits is largely unknown. Our aim was to investigate a role of genetic variants of FOXP2, a prominent speech and language gene, in dyslexia using imaging genetics. This technique combines functional magnetic resonance imaging (fMRI) and genetics to investigate relevance of genetic variants on brain activation. To our knowledge, this represents the first usage of fMRI-based imaging genetics in dyslexia. In an initial case/control study (n¼245) for prioritisation of FOXP2 polymorphisms for later use in imaging genetics, nine SNPs were selected. A non-synonymously coding mutation involved in verbal dyspraxia was also investigated. SNP rs12533005 showed nominally significant association with dyslexia (genotype GG odds ratio recessive model¼2.1 (95% confidence interval 1.1-3.9), P¼0.016). A correlated SNP was associated with altered expression of FOXP2 in vivo in human hippocampal tissue. Therefore, influence of the rs12533005-G risk variant on brain activity was studied. fMRI revealed a significant main effect for the factor 'genetic risk' in a temporo-parietal area involved in phonological processing as well as a significant interaction effect between the factors 'disorder' and 'genetic risk' in activation of inferior frontal brain areas. Hence, our data may hint at a role of FOXP2 genetic variants in dyslexia-specific brain activation and demonstrate use of imaging genetics in dyslexia research.

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

“…Indeed, the twin, segregation, aggregation, and gene candidate studies use phenotypes in their analyses to relate genetic mechanisms to their behavioral expression. The studies at the genetic level of analysis have shown that dyslexia is a heterogeneous disorder (e.g., Grigorenko et al, 1997; Raskind et al, 2012; Roeske et al, 2011; Schulte-Korne et al, 1998; Smith, Kimberling, Pennington, & Lubs, 1983; Smith-Spark, Fisk, Fawcett, & Nicolson, 2003; Velayos-Baeza, Levecque, Kobayashi, Holloway, & Monaco, 2010; Wigg et al, 2004; Wilcke et al, 2012). Likewise, phenotype studies of the behavioral markers show that dyslexia is a heterogeneous disorder (for review of the evidence, see Berninger & Richards, 2010; Raskind et al, 2012).…”

Ultrasonic vocalization changes and FOXP2 expression after experimental stroke

“…FOXP2 is highly conserved and its absence is associated with verbal dyspraxia in humans (5–8). Patients with heterozygous mutations in FOXP2 exhibit critical articulation deficits (8) and dyslexia (9). Foxp2 has also been implicated in the development of vocalization production in animals (9).…”

“…Patients with heterozygous mutations in FOXP2 exhibit critical articulation deficits (8) and dyslexia (9). Foxp2 has also been implicated in the development of vocalization production in animals (9). Absence of FOXP2 in mice manifests as motor impairment, abnormal cerebellar development and an absence of vocalization when exposed to stressors (10).…”

Working-memory endophenotype and dyslexia-associated genetic variant predict dyslexia phenotype

“…On the genetic level, several dyslexia-associated genes have been identified Carrion-Castillo et al, 2013;Kere, 2014;Wilcke et al, 2012).…”