In recent years there have been major advances in quantitative and molecular genetics. The overwhelming conclusion that has been reached in quantitative genetics is that genetic factors are important for most measures of adjustment. More surprisingly, genetic factors also have substantial influence on measures of family processes. Advances in genotyping, the identification of candidate genes, and the use of association strategies in molecular genetics have allowed for the investigation of associations between genes and continuously distributed characteristics, like adjustment. The proposed three-year project seeks to combine these advances to use candidate gene association to examine adolescent adjustment. In addition, this research will extend this strategy to explore the role of family processes in both moderating and mediating gene expression during adolescence. Genetic material (cheek scrapings) will be collected from two siblings (ages 10 to 18 at time 1) and both parents from the sample of 720 families who participated in the Nonshared Environment in Adolescent Development Project (NEAD). NEAD is a NIMH-sponsored project (MH-43373 and MH-48825), assessed twice, three years apart, focused on understanding adolescent adjustment and the role of genetic factors and family processes in shaping adjustment. This is the only quantitative genetic study that has intensively measured family processes, including observational assessments. The collection of genetic material from this sample will enable the examination of (1) candidate gene associations with adolescent adjustment, (2) longitudinal associations of candidate genes and adjustment, (3) family processes as moderators of gene expression (genotype-environment interactions), and (4) family processes as mediators of gene expression (genotype-environment correlations). The inclusion of siblings and parents will allow the use of control group strategies that are not affected by population stratification. For example, candidate gene associations will be conducted for one member of the sibling pair and the other sibling is then used for replication. Because the NEAD is a quantitative genetic sample, heritabilities can be computed to identify the most likely possibilities for association with candidate genes (i.e., those measures with the largest heritabilities are the best starting points). In addition, NEAD employed careful measurement of phenotypes, through the use of multi-measure, multi-agent assessment. This proposal, using the most recent advances in quantitative genetics and the most recent advances in molecular genetics has great potential for informing the question of how genes influence development.
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