QTL Mapping of Impulsivity-related Traits Before and After a Stressful Life Chang

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DESCRIPTION (provided by applicant): Impulsivity is a key feature of a large number of psychiatric disorders and psychosocial problems, including bipolar disorder, attention deficit hyperactivity disorder, conduct disorder, alcoholism, and substance abuse. Progress has been slow in identifying quantitative trait loci (QTL) and candidate genes that have consistent and significant effects on vulnerability for impulsivity-related disorders. New and more appropriate animal models are needed to augment current human studies to make progress in this important area of study. The proposed research will take advantage of the powerful Vervet Research Colony (VRC) pedigree and the recently developed vervet genetic linkage map and genomic tools to identify quantitative trait loci (QTL) for reliable and validated behavioral measures of impulsivity-related traits in a nonhuman primate model. The VRC pedigree contains up to 5 generations of phenotyped individuals in a single complex extended family. Variance components QTL analyses will be conducted on indices of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity, and Sociability for samples of up to 735 subjects using the vervet microsatellite linkage map. The discovery of putative QTL for the traits of interest will be followed up with high density mapping of the linkage region using SNP markers. This will be the first genome wide study of objectively measured, quantitative behavioral endophenotypes for impulsivity disorders in a nonhuman primate model. This study will also provide a unique opportunity to study the influence of the environment in the detection of susceptibility loci by comparing results from QTL analysis of behavioral traits in two different environments, before and after a stressful life change. Behavioral assessments of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity and Sociability will be repeated for a sample of 450 animals following cross country transport and relocation of the VRC to a new facility with more frequent handling and interventions. The transfer will allow us to compare the results of QTL analyses under baseline and more stressful environmental conditions to identify environment-specific QTL for the same impulsivity-related traits. This is a novel way of assessing the role of the gene-environment interactions in measuring effects of genetic variation on behavior traits