Genomewide scan for real-word reading subphenotypes of dyslexia: novel chromosome 13 locus and genetic complexity.
Dyslexia is a common learning disability exhibited as a delay in acquiring reading skills despite adequate intelligence and instruction. Reading single real words (real-word reading, RWR) is especially impaired in many dyslexics. We performed a genome scan, using variance components (VC) linkage analysis and Bayesian Markov chain Monte Carlo (MCMC) joint segregation and linkage analysis, for three quantitative measures of RWR in 108 multigenerational families, with follow up of the strongest signals with parametric LOD score analyses. We used single-word reading efficiency (SWE) to assess speed and accuracy of RWR, and word identification (WID) to assess accuracy alone. Adjusting SWE for WID provided a third measure of RWR efficiency. All three methods of analysis identified a strong linkage signal for SWE on chromosome 13q. Based on multipoint analysis with 13 markers we obtained a MCMC intensity ratio (IR) of 53.2 (chromosome-wide P < 0.004), a VC LOD score of 2.29, and a parametric LOD score of 2.94, based on a quantitative-trait model from MCMC segregation analysis (SA). A weaker signal for SWE on chromosome 2q occurred in the same location as a significant linkage peak seen previously in a scan for phonological decoding. MCMC oligogenic SA identified three models of transmission for WID, which could be assigned to two distinct linkage peaks on chromosomes 12 and 15. Taken together, these results indicate a locus for efficiency and accuracy of RWR on chromosome 13, and a complex model for inheritance of RWR accuracy with loci on chromosomes 12 and 15.
Igo
Robert P
RP
Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
Chapman
Nicola H
NH
Berninger
Virginia W
VW
Matsushita
Mark
M
Brkanac
Zoran
Z
Rothstein
Joseph H
JH
Holzman
Ted
T
Nielsen
Kathleen
K
Raskind
Wendy H
WH
Wijsman
Ellen M
EM
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010641:Phenotype