Gene Environment Interactions and Pre-disease Pathways

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Using four waves of data from Add Health, in this data analysis subproject we will examine the developmental trajectories of drug use and related behaviors, including conduct problems and risky sexual behavior. Genetic contributions will be examined in terms of their interaction with other biological, psychological, and social factors in a developmental life course framework. Attention to the developmental course and consequences of drug use leads to an emphasis on genetic polymorphisms in the dopamine system, some of which can be examined in detail through dense single nucleotide polymorphism (SNP) association studies of the candidate genes. Attention to the environmental influences on development leads to our simultaneous consideration of genotype by environment interactions, and to a consideration of genetic polymorphisms of the serotonin system that may mediate responses to environmental stressors and life transitions. We will: empirically determine trajectories of substance use and abuse from adolescence into young adulthood, and identify subgroups of individuals who reflect distinct patterns of continuity and change in substance use over time; describe how trajectories of substance use intersect with patterns of sexual risk taking and anti-social behavior; examine trajectories of substance use, and their covariation with sexual and anti-social behavior patterns, by gender and race/ethnicity to determine if there are patterns that are more characteristic of some groups versus others; examine genetic contributions to substance use trajectories and related health outcomes through biometrical analyses of the genetic pairs data; examine genetic contributions to substance use trajectories and related health outcomes through association tests of candidate genes including dense SNP mapping of specific target genes in the dopaminergic pathways implicated in the response to substances of abuse, and serotonergic pathways implicated in response to environmental stressors or adversity; examine gene X environment interactions in predicting the trajectories of substance use, and associated conduct problems, risky sexual behavior and related health outcomes, and whether these interactions vary by gender or race/ethnicity.