Heritable Composite Phenotypes Defined by Combinations of Conduct Problem, Depression, and Temperament Features: Contributions to risk for Alcohol Problems.

Abstract

The genetic architectures underlying symptoms of conduct problems and depression have largely been examined separately and without incorporating temperament, despite evidence for their genetic overlap. We examined how symptoms and temperament dimensions were transmitted together in families to identify highly heritable composite phenotypes, and how these composite phenotypes predicted alcohol outcomes in young adulthood. Participants (N = 486) were drawn from the third generation of families oversampled for alcohol use disorder in the first generation. Conduct problems, depression, and temperament were reported at 11-19 years old and alcohol outcomes at 18-26 years old. Using principal components of heritability analysis, we found seven highly heritable composite phenotypes, five of which predicted alcohol outcomes: three characterized by co-occurring conduct problems and depression and two by conduct problems. Novel composite phenotypes that were characterized by both conduct problems and depression showed different types of symptoms, temperament features, and genetic underpinnings. Children manifesting differing composite phenotypes might benefit from distinct treatments based on their unique etiologies.