The proposed study is a continuation of a four-year investigation of the influence of quantitative trait loci (QTL) on normal behavioral development. The primary objective is to conduct a genome-wide search for genes that influence developmental variations in human temperament, personality and cognition. The project will expand on the original sample by continuing to draw from a sample of twin sibships born between 1959 and 1994 whose development has been studied longitudinally during infancy and childhood, as well as from 110 sibships whose parents were tested as children in the Louisville Twin Study (LTS). Years 5 to 8 of the study will involve behavioral testing (2290 child visits, 740 adult visits), blood collection (1240 blood samples), and genotyping at 200 polymorphic markers in 2350 DNA samples. Across Years 1 to 8, 445 families, 2515 individuals, and 2300 sibling comparisons will be involved in the analyses. Sib-pair linkage analysis for the different behavioral traits will be conducted by comparing behavioral similarity within and between twin and sib pairs to the proportion of alleles shared by the pairs (i.b.d.) at the markers using a modified version of the D-F regression approach developed by Fulker and DeFries. If linkage is found, then the second step will be to use i.b.d. estimates at a series of points equally spaced at 1 or 2 cMs along the chromosome among the markers to locate the most likely position of the QTL. When a QTL is identified, or a set of linkages is found for a set of correlated traits, then maximum-likelihood models will be fit to the multi-trait data using the estimated sets of pair i.b.d. values. Existing quantitative genetic pedigree models will be extended to incorporate the information on shared alleles to study the timing and specificity of gene action, estimate the effects of shared and nonshared environmental influences, and to assess the impact of assortative mating on genetic and environmental parameter estimates.
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