A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia

Recent application of nonparametric-linkage analysis to reading disability has implicated a putative quantitative-trait locus (QTL) on the short arm o f chromosome 6. In the present study, we use QTL methods to evaluate linkag e to the 6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear fami lies that were selected on the basis of a dyslexic proband. We have assesse d linkage directly for several quantitative measures that should correlate with different components of the phenotype, rather than using a single comp osite measure or, employing categorical definitions of subtypes, Our measur es include the traditional IQ/reading discrepancy score, as well as tests o f word recognition, irregular-word reading, and nonword reading. Pointwise analysis by means of sib-pair trait differences suggests the presence, in 6 p21.3, of a QTL influencing multiple components of dyslexia, in particular the reading of irregular words (P =.0016) and nonwords (P =,0024). A comple mentary statistical approach involving estimation of variance components su pports these findings (irregular words, P=.007; nonwords, P=.0004). Multipo int analyses place the QTL within the D6S422-D6S291 interval, with a peak a round markers D6S276 and D6S105 consistently identified by approaches based on trait differences (irregular words, P=.00035; nonwords, P =.0035) and v ariance components (irregular words, P =.007; nonwords, P =.0038). Our find ings indicate that the QTL affects both phonological and orthographic skill s and is not specific to phoneme awareness, as has been previously suggeste d. Further studies will be necessary to obtain a more precise localization of this QTL, which may lead to the isolation of one of the genes involved i n developmental dyslexia.