[show abstract][hide abstract] ABSTRACT: Twin studies have provided evidence for shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) and specific reading disabilities (RD), with this overlap being highest for the inattentive symptom dimension of ADHD. Previously, we found evidence for association of the dopamine receptor D1 gene (DRD1) with ADHD, and with the inattentive symptom dimension in particular. This, combined with evidence for working memory (WM) deficits in individuals with RD or ADHD, and the importance of D1 receptors in attentional processes and WM function, suggests that DRD1 may be a common genetic influence underlying both disorders. Here, in a study of 232 families ascertained through probands with reading problems, we tested for association of the DRD1 gene with RD, as a categorical trait, and with quantitative measures of key reading component skills, WM ability, and inattentive symptoms. Although no associations were found with RD, or with reading component skills or verbal WM, we found evidence for association with inattentive behaviour. Specifically, DRD1 Haplotype 3, the haplotype previously found to be associated with inattentive symptoms in ADHD, is also associated with parent- and teacher-reported symptoms of inattention in this sample selected for reading problems (P=0.023 and 0.004, respectively). Together, the replicated finding of Haplotype 3 association with inattentive symptoms in two independent study samples strongly supports a role for DRD1 in attentional ability. Furthermore, the association of DRD1 with inattention, but not with RD, or the other reading and reading-related phenotypes analysed, suggests that DRD1 contributes uniquely to inattention, without overlap for reading ability.
[show abstract][hide abstract] ABSTRACT: Dyslexia has been linked to a number of chromosomal regions including 15q. Recently a gene, EKN1, with unknown function in the linked region, was identified via a translocation breakpoint. This gene was further supported as a susceptibility locus by association studies in a Finnish sample. We investigated the possibility of this locus as a susceptibility gene contributing to dyslexia, analyzed as a categorical trait, and analyzed key reading phenotypes as quantitative traits using six polymorphisms including the two previously reported to be associated with dyslexia. In our sample of 148 families identified through a proband with reading difficulties, we found significant evidence for an association to dyslexia analyzed as a categorical trait and found evidence of association to the reading and related processes of phonological awareness, word identification, decoding, rapid automatized naming, language ability, and verbal short-term memory. However, association was observed with different alleles and haplotypes than those reported to be associated in a Finnish sample. These findings provide support for EKN1 as a risk locus for dyslexia and as contributing to reading component processes and reading-related abilities. Based on these findings, further studies of this gene in independent samples are now required to determine the relationship of this gene to dyslexia.