DCDC2, KIAA0319 and CMIP are associated with reading-related traits

Abstract

Background: Several susceptibility genes have been proposed for dyslexia (reading disability; RD) and specific language impairment (SLI). RD and SLI show comorbidity, but it is unclear whether a common genetic component is shared.

Methods: We have investigated whether candidate genes for RD and SLI affect specific cognitive traits or have broad effect on cognition. We have analyzed common risk variants within RD (MRPL19/C2ORF3, KIAA0319, and DCDC2) and language impairment (CMIP and ATP2C2) candidate loci in the Avon Longitudinal Study of Parents and Children cohort (n = 3725), representing children born in southwest England in the early 1990s.

Results: We detected associations between reading skills and KIAA0319, DCDC2, and CMIP. We show that DCDC2 is specifically associated with RD, whereas variants in CMIP and KIAA0319 are associated with reading skills across the ability range. The strongest associations were restricted to single-word reading and spelling measures, suggesting that these genes do not extend their effect to other reading and language-related skills. Inclusion of individuals with comorbidity tends to strengthen these associations. Our data do not support MRPL19/C2ORF3 as a locus involved in reading abilities nor CMIP/ATP2C2 as genes regulating language skills.

Conclusions: We provide further support for the role of KIAA0319 and DCDC2 in contributing to reading abilities and novel evidence that the language-disorder candidate gene CMIP is also implicated in reading processes. Additionally, we present novel data to evaluate the prevalence and comorbidity of RD and SLI, and we recommend not excluding individuals with comorbid RD and SLI when designing genetic association studies for RD.

Figure 1

Diagram illustrating how phenotypic subgroups were identified. The subgroups above the black horizontal lines were used for quantitative analysis while the ones below were used for case-control analysis. The extent of co-morbidity (hence the non-mutually exclusive definition of cases), can be seen in Figure 2. ADHD, attention-deficit/hyperactivity disorder; CCC_SUM7, sum of first seven scales from the Children's Communication Checklist; PERF_IQ, performance IQ; RD, reading disability; SLI, specific language impairment.

Figure 2

A Venn diagram illustrating the distributions of the cases identified for reading disabilities (RD), specific language impairment (SLI), and attention-deficit/hyperactivity disorder (ADHD) from Sample F1. Circle size is proportional to sample size, and circle overlaps represent comorbidity.