Linkage analyses of four regions previously implicated in dyslexia: confirmation of a locus on chromosome 15q.

Abstract

Dyslexia is a common, complex disorder, which is thought to have a genetic component. There have been numerous reports of linkage to several regions of the genome for dyslexia and continuous dyslexia-related phenotypes. We attempted to confirm linkage of continuous measures of (1) accuracy and efficiency of phonological decoding; and (2) accuracy of single word reading (WID) to regions on chromosomes 2p, 6p, 15q, and 18p, using 111 families with a total of 898 members. We used both single-marker and multipoint variance components linkage analysis and Markov Chain Monte Carlo (MCMC) joint segregation and linkage analysis for initial inspection of these regions. Positive results were followed with traditional parametric lod score analysis using a model estimated by MCMC segregation analysis. No positive linkage signals were found on chromosomes 2p, 6p, or 18p. Evidence of linkage of WID to chromosome 15q was found with both methods of analysis. The maximum single-marker parametric lod score of 2.34 was obtained at a distance of 3 cM from D15S143. Multipoint analyses localized the putative susceptibility gene to the interval between markers GATA50C03 and D15S143, which falls between a region implicated in a recent genome screen for attention-deficit/hyperactivity disorder, and DYX1C1, a candidate gene for dyslexia. This apparent multiplicity of linkage signals in the region for developmental disorders may be the result of errors in map and/or model specification obscuring the pleiotropic effect of a single gene on different phenotypes, or it may reflect the presence of multiple genes.