Abstract
A number of candidate genes for reading and language impairment have been replicated, primarily in samples of children with developmental disability or delay, although these genes are also supported in adolescent population samples. The present study used a systematic approach to test 14 of these candidate genes for association with reading assessed in late adulthood (two cohorts with mean ages of 70 and 79 years). Gene-sets (14 candidates, axon-guidance and neuron migration pathways) and individual SNPs within each gene of interest were tested for association using imputed data referenced to the 1000 genomes European panel. Using the results from the genome-wide association (GWA) meta-analysis of the two cohorts (N = 1217), a competitive gene-set analysis showed that the candidate gene-set was associated with the reading index (p = .016) at a family wise error rate corrected significance level. Neither axon guidance nor neuron migration pathways were significant. Whereas individual SNP associations within CYP19A1, DYX1C1, CNTNAP2 and DIP2A genes (p < .05) did not reach corrected significance their allelic effects were in the same direction as past available reports. These results suggest that reading skill in normal adults shares the same genetic substrate as reading in adolescents, and clinically disordered reading, and highlights the utility of adult samples to increase sample sizes in the genetic study of developmental disorders.
Highlights
Reading performance is highly heritable (Bates et al 2004; Hayiou-Thomas et al 2010), making the genetic study of this skill important for understanding the causes of disorders in these abilities (Fisher and DeFries 2002)
The QQ plot for the reading component (Fig. 1) is shown for all SNPs lying within the dyslexia candidate genes of interest; see online Fig. 1 for verbal executive processing
Within DYX1C1, known as Dynein Axonemal Assembly Factor 4 (DNAAF4), the direction of allelic effect for rs3743204 was consistent with Bates et al (2010), and Becker et al (2014) who found the minor allele associated with better reading scores in respective population and reading-impaired samples
Summary
Reading performance is highly heritable (Bates et al 2004; Hayiou-Thomas et al 2010), making the genetic study of this skill important for understanding the causes of disorders in these abilities (Fisher and DeFries 2002). A barrier to large-scale investment in this approach is that it is currently unknown whether reading disorder in adults follows the same genetic pattern as in children, or even if genes associated with reading replicate in older adults, with many years of practice at the skill. To validate this approach, here, we tested association between 14 candidate genes—implicated in reading impairment— and reading ability in two elderly cohorts
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