The Association of Dyslexia and Developmental Speech and Language Disorder Candidate Genes with Reading and Language Abilities in Adults

Abstract

Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.

Dyslexia and cognitive impairment in adult patients with myotonic dystrophy type 1: a clinical prospective analysis

“…Finally, whether specific RNA splicing events, e.g. of the FOXP2 gene, a gene implicated in speech and language disorders, may contribute to this dyslexic features remain presently open [33].…”

The Polygenic Nature and Complex Genetic Architecture of Specific Learning Disorder

“…Doust et al performed gene-set-based analysis for reading impairment candidate genes and for the Gene Ontology biological pathway genes for ‘axon guidance’ and ‘neuron migration’. The lack of replication of previous associations in this carefully characterized, yet unselected for SLD/dyslexia, cohort could be true or could be attributed to a number of other reasons: lack of statistical power to detect variants of small effect size, despite being one of the largest cohorts analyzed for reading abilities thus far, or sampling bias owing to participants’ recruitment from a twin registry [ 75 ].…”

“…Original studies also failed to find associations supporting the neuronal migration, axon guidance or steroid hormone-related pathways [ 75 , 104 , 109 , 128 ]. Thus, it emerges that although researchers have been keen to place many of the dyslexia candidate genes in a theoretical molecular/cellular model network involved in neuronal migration and neurite outgrowth, it seems unlikely that there is just a single explanatory model that connects all dyslexia-associated proteins on the molecular level.…”

Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders

“…For dyslexia/SLI, we found ATP2C2 (Newbury et al, 2011;Müller et al, 2017;Martinelli et al, 2021), CCDC136 (Gialluisi et al, 2014;Adams et al, 2017), CMAHP (Eicher et al, 2014), CMIP (Newbury et al, 2011;Scerri et al, 2011;Luciano et al, 2018), CNTNAP2 (Newbury et al, 2011;Peter et al, 2011;Eicher et al, 2013;Luciano et al, 2018), COL4A2 (Eicher et al, 2013), FLNC (Gialluisi et al, 2014;Adams et al, 2017), FOXP2 (Peter et al, 2011;Wilcke et al, 2012;Eicher et al, 2013;Mozzi et al, 2017;Sánchez-Morán et al, 2018;Doust et al, 2020), KIAA0319 (Couto et al, 2010;Czamara et al, 2011;Elbert et al, 2011;König et al, 2011;Newbury et al, 2011;Scerri et al, 2011;Cope et al, 2012;Zou et al, 2012;Eicher et al, 2013Eicher et al, , 2014Powers et al, 2013Powers et al, , 2016Mascheretti et al, 2015;Adams et al, 2017;Carrion-Castillo et al, 2017;Neef et al, 2017;Centanni et al, 2018;Luciano et al, 2018;…”