The effect of dyslexia candidate genes on reading and language abilities in an adult population cohort

Reading and language abilities are critical factors for educational achievement and success in adulthood. These traits are highly heritable, but their underlying genetic architecture is largely undetermined. Genetic studies of reading and language traditionally focus on children with developmental disorders, however unselected adult samples would provide larger sample sizes thereby increasing power to identify genetic factors of small effect size. Here, we introduce an Australian adult population cohort (42 – 73 years of age, N = 1,195) with validated measures of reading and language ability, including non-word reading to assess phonological processing: a core component of reading skill. Genome-wide association was performed for a reading and spelling composite score, non-word reading, phonetic spelling, non-word repetition (a marker of language ability), and self-reported reading impairment. Here we focus only on replicating previous single nucleotide polymorphisms (SNPs) and genes associated with dyslexia and specific language impairments (SLI), for which we are sufficiently powered. In gene-based tests, FOXP2, a well-established language gene, was identified in the top three most significant genes for non-word repetition (p = 1.21 x 10-4). The dyslexia candidates MRPL19 and S100B were significantly associated with phonetic spelling (p = 3.11 x 10-2) and non-word repetition (p =4.58 x 10-2) respectively. For the reading and spelling composite score, SNPs rs9722 and rs9467075, previously associated with dyslexia, were significant (p = 1.67 x 10-2; 2.27 x 10-2 respectively) and seven further previously-reported SNPs (rs17236239, rs2710102, rs759178, rs600753, rs2538976, rs2538991 and rs807701) were significantly associated with non-word reading. Gene-set analyses of 14 candidate dyslexia genes and five SLI genes were not significant, but the neuron migration pathway was significantly associated with the composite reading and spelling score (p = 3.68 x 10-2). This research contributes to the identification and replication of genetic factors in reading and language disorders, crucial for understanding their aetiology and informing intervention strategies.