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Tier I

1680

GS128591: Average rotarod training latency Chr# 5

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1275

GS400080: The differentially expressed genes (DEGs) involved in 7 days of withdrawal after chronic cocaine treatment in mice (RNA-seq)

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GS405734: WWP1 KO vs WT

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GS407721: Blood gene expression signatures of chronic intermittent ethanol consumption in mice in females q-value

Figure Label:	Alcohol blood gene expression in females q-value
Description:	Alcohol Use Disorder (AUD) is a chronic, relapsing syndrome diagnosed by a heteroge- neous set of behavioral signs and symptoms. There are no laboratory tests that provide direct objective evidence for diagnosis. Microarray and RNA-Seq technologies enable genome-wide transcriptome profiling at low costs and provide an opportunity to identify bio- markers to facilitate diagnosis, prognosis, and treatment of patients. However, access to brain tissue in living patients is not possible. Blood contains cellular and extracellular RNAs that provide disease-relevant information for some brain diseases. We hypothesized that blood gene expression profiles can be used to diagnose AUD. We profiled brain (prefrontal cortex, amygdala, and hypothalamus) and blood gene expression levels in C57BL/6J mice using RNA-seq one week after chronic intermittent ethanol (CIE) exposure, a mouse model of alcohol dependence. We found a high degree of preservation (rho range: [0.50, 0.67]) between blood and brain transcript levels. There was small overlap between blood and brain DEGs, and considerable overlap of gene networks perturbed after CIE related to cell- cell signaling (e.g., GABA and glutamate receptor signaling), immune responses (e.g., anti- gen presentation), and protein processing / mitochondrial functioning (e.g., ubiquitination, oxidative phosphorylation). Blood gene expression data were used to train classifiers (logis- tic regression, random forest, and partial least squares discriminant analysis), which were highly accurate at predicting alcohol dependence status (maximum AUC: 90.1%). These results suggest that gene expression profiles from peripheral blood samples contain a bio- logical signature of alcohol dependence that can discriminate between CIE and Air subjects.
Authors:	Laura B Ferguson, Amanda J Roberts, R Dayne Mayfield, Robert O Messing

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351