Segregation analysis of phenotypic components of learning disabilities. I.Nonword memory and digit span

Dyslexia is a common and complex disorder with evidence for a genetic compo nent. Multiple loci (i.e., quantitative-trait loci [QTLs]) are likely to be involved, but the number is unknown. Diagnosis is complicated by the lack of a standard protocol, and many diagnostic measures have been proposed as understanding of the component processes has evolved. One or more genes may , in turn, influence these measures. To date, little work has been done to evaluate the mode of inheritance of individual component-as opposed to comp osite-phenotypes, beyond family or twin correlation studies that initially demonstrate evidence for a genetic basis of such components. Here we use tw o approaches to segregation analysis in 102 nuclear families to estimate ge netic models for component phenotypes associated with dyslexia: digit span and a nonword-repetition task. Both measures are related to phonological sk ills, one of the key component processes in dyslexia. We use oligogenic-tra it segregation analysis to estimate the number of QTLs contributing to each phenotype, and we use complex segregation analysis to identify the most pa rsimonious inheritance models. We provide evidence in support of both a maj or-gene mode of inheritance for the nonword-repetition task, with similar t o 2.4 contributing QTLs, and for a genetic basis of digit span, with simila r to 1.9 contributing QTLs. Results obtained by reciprocal adjustment of me asures suggest that genes contributing to digit span may contribute to the nonword-repetition score but that there are additional QTLs involved in non word repetition. Our study adds to existing studies of the genetic basis of composite phenotypes related to dyslexia, by providing evidence for major- gene modes of inheritance of these single-measure component phenotypes.