The proposed research is the competitive renewal of an NIMH MERIT award focused on the linguistic phenotype in familial dyslexia. Our earlier work has clarified both the underlying cognitive phenotype and the genetic etiology of familial dyslexia. We propose to extend that work by examining both the phenotypic and genotypic relation between dyslexia (or reading disability--RD) and phonological disorder (PD), which manifest at different ages but exhibit several intriguing commonalities. The two disorders overlap symptomatically in that some prospective studies of children with PD find they later have an elevated rate of RD and in that retrospective studies of children with RD document elevated rates of earlier PD. The underlying cognitive phenotype that is characteristic of RD, a deficit in phoneme awareness, is also found on follow-up in many cases of PD. Finally, there is evidence that each disorder is under genetic influence and that the two disorders are co-familial. In sum, there is evidence for overlap at three levels of analysis: defining symptoms, underlying cognitive processes, and familial etiology. We will test five competing explanations for this overlap: 1) that they are the same disorder in terms of both genetic etiology and cognitive phenotype, but that the symptom manifestations differ depending on severity such that PD + RD is a more severe manifestation than RD alone; 2) that they share a common etiology which acts pleiotropically to produce either PD, RD, or both in a given individual; 3) that PD and RD have distinct etiologies, but share a common cognitive phenotype (cognitive phenocopy hypothesis); 4) that PD and RD have distinct etiologies, but that PD accompanied by specific language impairment develops into a symptom phenocopy of RD (synergy hypothesis); or 5) that PD and RD have distinct etiologies, but co-occur in offspring because of assortment (RD individuals are more likely to mate with PD individuals). We will perform four principal tests to distinguish these hypotheses. Specifically, we will test 1) whether there is a common cognitive phenotype by means of a longitudinal study; 2) whether there is a common genetic etiology by means of a linkage analysis of PD families; 3) whether there is assortment by examining parents of PD and RD children; and 4) how PD, RD, and PD+RD segregate in families.
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