DCDC2 genetic variants and susceptibility to developmental dyslexia

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Abstract
Objective(s) Developmental dyslexia is a heritable condition, with genetic factors accounting for 44–75% of the variance in performance tests of reading component subphenotypes. Compelling genetic linkage and association evidence supports a quantitative trait locus in the 6p21.3 region that encodes a gene called DCDC2. In this study, we explored the contribution of two DCDC2 markers to dyslexia, related reading and memory phenotypes in nuclear families of Italian origin. Methods The 303 nuclear families recruited on the basis of having a proband with developmental dyslexia have been studied with 6p21.3 markers, BV677278 and rs793862. Marker-trait association was investigated by the quantitative transmission disequilibrium test (version 2.5.1) that allows for the analyses of quantitative traits. Seven phenotypes were used in association analyses, that is, word and nonword reading, word and nonword spelling, orthographic choice, memory, and the affected status based on inclusion criteria. Results Quantitative transmission disequilibrium test analyses yielded evidence for association between reading skills and the BV677278 deletion (empirical P-values=0.025–0.029) and between memory and BV677278 allele 10 (empirical P-value=0.0001). Conclusion Our result adds further evidence in support of DCDC2 contributing to the deficits in developmental dyslexia. More specifically, our data support the view that DCDC2 influences both reading and memory impairments thus shedding further light into the etiologic basis and the phenotypic complexity of developmental dyslexia.