Consistent with the Overall aims of the PARC, Core C002 will focus on robust identification of genes and gene networks involved in the etiology of ethanol use disorders by studying naturally occurring variation in voluntary ethanol preference/consumption, and will also study genetic contributions to the consequences of ethanol use. Priority for expression and sequence comparisons will be determined based on several criteria, including putative biological role and likely relevance to ethanol action. QPCR, PCR, and sequencing will be used to confirm initial co-expression and co-splicing identified in mice and non-human primate model systems, prior to experimental perturbation and validation. C002 will be active in all years of requested Center support, and will continue to focus on biostatistics and bioinformatics support, as well as continuing to provide critical expertise in sample and library preparation and initial confirmation to aid in prioritization of targets for the Validation Core C001. Core C002 plays a critical role for data integration of the diverse readouts generated by the Projects (e.g., expression, genetic variants, epigenetics, imaging, behavioral phenotypes) that is necessary in order to elucidate the underlying relevant brain circuitry and changes in the brain that are relevant to genetic risk for alcohol use as well as the consequences of use. This Core will facilitate hypothesis-driven (candidate gene) and hypothesis-generating (network) analyses to address the Center goals. In some cases an underlying candidate gene may be the same in animal models (mice or nonhuman primates) and humans and will be prioritized for further study. In other cases, animal model research may identify a gene network relevant in humans, with a hub that could be manipulated to examine network effects. Analyses of both candidate genes and networks will be more powerful than either alone to provide the interlocking levels of proof to move from gene/network to mechanism, and better prevent and treat alcohol abuse/dependence by identifying new risk factors associated with chronic alcohol abuse use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA010760-23
Application #
9404929
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
23
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Mangold, Colleen A; Wronowski, Benjamin; Du, Mei et al. (2017) Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging. J Neuroinflammation 14:141
Nimitvilai, Sudarat; Uys, Joachim D; Woodward, John J et al. (2017) Orbitofrontal Neuroadaptations and Cross-Species Synaptic Biomarkers in Heavy-Drinking Macaques. J Neurosci 37:3646-3660
Hasler, Brant P; Franzen, Peter L; de Zambotti, Massimiliano et al. (2017) Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study. Alcohol Clin Exp Res 41:1154-1165
Allen, Daicia C; Ford, Matthew M; Grant, Kathleen A (2017) Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol. Curr Top Behav Neurosci :
Colville, A M; Iancu, O D; Oberbeck, D L et al. (2017) Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice. Genes Brain Behav 16:462-471
Jones, Scott A; Steele, Joel S; Nagel, Bonnie J (2017) Binge drinking and family history of alcoholism are associated with an altered developmental trajectory of impulsive choice across adolescence. Addiction 112:1184-1192
Böger, Carsten A; Gorski, Mathias; McMahon, Gearoid M et al. (2017) NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality. J Am Soc Nephrol 28:2311-2321
Beattie, Matthew C; Maldonado-Devincci, Antoniette M; Porcu, Patrizia et al. (2017) Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3?,5?)3-hydroxypregnan-20-one (3?,5?-THP) in the amygdala of the cynomolgus monkey. Addict Biol 22:318-330
Jimenez, Vanessa A; Allen, Daicia C; McClintick, Megan N et al. (2017) Social setting, social rank and HPA axis response in cynomolgus monkeys. Psychopharmacology (Berl) 234:1881-1889
Buck, Kari J; Chen, Gang; Kozell, Laura B (2017) Limbic circuitry activation in ethanol withdrawal is regulated by a chromosome 1 locus. Alcohol 58:153-160

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