Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice.

Mouse behavioral genetic mapping studies can identify genomic intervals modulating complex traits under well-controlled environmental conditions and have been used to study ethanol behaviors to aid in understanding genetic risk and the neurobiology of alcohol use disorder (AUD). However, historically such studies have produced large confidence intervals, thus complicating identification of potential causal candidate genes. Diversity Outbred (DO) mice offer the ability to perform high-resolution quantitative trait loci (QTL) mapping on a very genetically diverse background, thus facilitating identification of candidate genes.

Characterizing the longitudinal course of symptoms and functioning in bipolar disorder.

Background: The course of Bipolar Disorder (BD) is highly variable, with marked inter and intra-individual differences in symptoms and functioning. In this study, we identified illness trajectories across major clinical domains that could have etiological, prognostic, and therapeutic relevance.

Methods: Using the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we performed univariate and multivariate trajectory modeling of depressive symptoms, manic symptoms, and psychosocial functioning.

Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data.

Genome-wide association studies on alcohol dependence, by themselves, have yet to account for the estimated heritability of the disorder and provide incomplete mechanistic understanding of this complex trait. Integrating brain ethanol-responsive gene expression networks from model organisms with human genetic data on alcohol dependence could aid in identifying dependence-associated genes and functional networks in which they are involved. This study used a modification of the Edge-Weighted Dense Module Searching for genome-wide association studies (EW-dmGWAS) approach to co-analyze whole-genome gene expression data from ethanol-exposed mouse brain tissue, human protein-protein interaction databases and alcohol dependence-related genome-wide association studies.

Beyond genome-wide significance: integrative approaches to the interpretation and extension of GWAS findings for alcohol use disorder.

Alcohol use disorder (AUD) is a heritable complex behavior. Due to the highly polygenic nature of AUD, identifying genetic variants that comprise this heritable variation has proved to be challenging. With the exception of functional variants in alcohol metabolizing genes (e.

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans.