Unlike simple single-gene genetic disorders, dimensions of cognitive abilities are influenced by many genes and by appreciable environmental factors as well. Such multiple-gene, multifactorial dimensions of behavior represent a challenge for the application of the new molecular genetic techniques. The proposed three-year project will screen over 100 genetic markers, especially those associated with neurological function, in a sample of more than 600 children tested on a wide range of cognitive abilities in order to identify associations between genetic markers and cognitive abilities in children, even when such associations account for only a small amount of variance. Blood will be obtained and permanent cell lines established. Genetic markers will be assessed from genomic DNA obtained from the permanent cell lines. These genetic marker data will be used in association analyses with cognitive data that have already been obtained for these children (at 6 to 12 years of age) on an extensive battery of information-processing tasks, psychometric tests, and school achievement tests, yielding hundreds of cognitive variables as part of an NICHD-funded project (HD-21947). The 600 children are members of 300 same-sex pairs of twins, which circumstances make possible (1) estimates of genetic influence for each of the cognitive variables for this specific sample, and (2) exploration of associations between genetic markers and cognitive abilities for one member of each twin pair and replication of associations using the other half-sample. The large sample size will make it possible to detect significant associations between genetic markers and cognitive abilities that account individually for as little as 1% of the variance but with substantial effects in the aggregate. The availability of data for many cognitive variables greatly increases the chances of finding associations with a particular genetic marker. Multivariate analysis of many genetic markers permits the identification of combinations of genetic markers that are associated with cognitive abilities. The permanent cell lines will provide an unlimited supply of DNA for the proposed RFLP analyses, as well as a permanent resource for future DNA studies of cognitive abilities using this sample. The synergism created by the merger of quantitative genetics and molecular genetics has great potential to advance our understanding of cognitive development in children.
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