An investigation into the genetic etiology of adolescent antisocial behavior and conduct disorder: An application of item response theory

It is generally accepted that antisocial behavior is both environmentally and genetically influenced. However, to date, specific genes contributing to the etiology of antisocial behavior have not been identified. Linkage and association analyses designed to identify specific chromosomal regions or genes that contribute to a variety of complex behavioral traits have for the most part resulted in non-replication or null results. While the statistical models and molecular genetic methods have kept pace with the advancements in the field of behavioral genetics, the importance of, and methodology for refining phenotypes has been largely ignored.; This dissertation presents behavior genetic and linkage analyses for adolescent antisocial behavior with specific emphasis on DSM-IV Conduct Disorder (CD) criteria. The goal of this body of research is to define and employ an optimal phenotype for genetic linkage analysis. Univariate genetic analyses of twin data were used to estimate the relative influence of genes and the environment on CD at the level of the full scale, aggressive and non-aggressive domains, and on individual symptoms. A bivariate analysis was used to determine the extent to which shared or unique genetic and environmental factors influence the aggressive and non-aggressive domains of CD. Based on findings from the twin analyses of the CD phenotype, it appears that improvements could be made to the common model based on summing up all of the CD symptoms to derive a continuous phenotype. Item Response Theory (IRT) is proposed as a method that may prove useful for refining and obtaining continuous phenotypes. The IRT methodology is employed to identify items that are appropriate for application to a sample of selected probands and their siblings in a genome-wide scan for chromosomal regions influencing CD. Results of the genome scan suggest that there may be a region on the short arm of Chromosome 9 associated with adolescent antisocial behavior. The utility, advantages, and disadvantages of IRT as a tool for refining phenotypes are discussed.