Pleiotropic effects of DCDC2 and DYX1C1 genes on language and mathematics traits in nuclear families of developmental dyslexia.

Converging evidence indicates that developmental problems in oral language and mathematics can predate or co-occur with developmental dyslexia (DD). Substantial genetic correlations have been found between language, mathematics and reading traits, independent of the method of sampling. We tested for association of variants of two DD susceptibility genes, DCDC2 and DYX1C1, in nuclear families ascertained through a proband with DD using concurrent measurements of language and mathematics in both probands and siblings by the Quantitative Transmission Disequilibrium Test. Evidence for significant associations was found between DCDC2 and 'Numerical Facts' (p value = 0.02, with 85 informative families, genetic effect = 0.57) and between 'Mental Calculation' and DYX1C1 markers -3GA (p value = 0.05, with 40 informative families, genetic effect = -0.67) and 1249GT (p value = 0.02, with 49 informative families, genetic effect = -0.65). No statistically significant associations were found between DCDC2 or DYX1C1 and language phenotypes. Both DCDC2 and DYX1C1 DD susceptibility genes appear to have a pleiotropic role on mathematics but not language phenotypes.