Human variation in alcohol response is influenced by variation in neuronal signaling genes.
paper
Cited
Public
Unavailable
- Authors
- Joslyn, Geoff; Ravindranathan, Ajay; Brush, Gerry; Schuckit, Marc; White, Raymond L
- Year
- 2010
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 20201926
- DOI
- 10.1111/j.1530-0277.2010.01152.x
BACKGROUND: Alcohol use disorders (AUD) exhibit the properties shared by common conditions and diseases classified as genetically complex. The etiology of AUDs is heterogeneous involving mostly unknown interactions of environmental and heritable factors. A person's level of response (LR) to alcohol is inversely correlated with a family history and the development of AUDs. As an AUD endophenotype, alcohol LR is hypothesized to be less genetically complex and closer to the primary etiology of AUDs. METHODS: A genome wide association study (GWAS) was performed on subjects characterized for alcohol LR phenotypes. Gene Set Enrichment Analysis (GSEA) of the GWAS data was performed to determine whether, as a group, genes that participate in a common biological function (a gene set) demonstrate greater genetic association than would be randomly expected. RESULTS: The GSEA analysis implicated variation in neuronal signaling genes, especially glutamate signaling, as being involved in alcohol LR variability in the human population. CONCLUSIONS: These data, coupled with cell and animal model data implicating neuronal signaling in alcohol response, support the conclusion that neuronal signaling is mechanistically involved in alcohol's cellular and behavioral effects. Further, these data suggest that genetic variation in these signaling pathways contribute to human variation in alcohol response. Finally, this concordance of the cell, animal, and human findings supports neuronal signaling, particularly glutamate signaling, as a prime target for translational studies to understand and eventually modulate alcohol's effects.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Modeling Brain Gene Expression in Alcohol Use Disorder with Genetic Animal Models. | Hitzemann R et al. | β | 2025 | β |
| Genetic influences on alcohol sensitivity: A critical review. | Yeung EW et al. | β | 2024 | β |
| Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects. | Shetty AC et al. | β | 2024 | β |
| "Weeding out" violence? Translational perspectives on the neuropsychobiological links between cannabis and aggression. | Bortolato M et al. | β | 2024 | β |
| Genetic overlap between mood instability and alcohol-related phenotypes suggests shared biological underpinnings | Icick R et al. | β | 2022 | β |
| Genetic overlap between mood instability and alcohol-related phenotypes suggests shared biological underpinnings. | Icick R et al. | β | 2022 | β |
| Structure-activity studies of PTPRD phosphatase inhibitors identify a 7-cyclopentymethoxy illudalic acid analog candidate for development. | Henderson IM et al. | β | 2022 | β |
| On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption. | Hitzemann R et al. | β | 2021 | β |
| Susceptibility to extinction and reinstatement of ethanol-induced conditioned place preference is related to differences in astrocyte cystine-glutamate antiporter content. | Amaral VCS et al. | β | 2021 | β |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | β | 2020 | β |
| Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism. | Lathen DR et al. | β | 2020 | β |
| A Pathway-Based Genomic Approach to Identify Medications: Application to Alcohol Use Disorder. | Ferguson LB et al. | β | 2019 | β |
| Brain Imaging-Guided Analysis Reveals DNA Methylation Profiles Correlated with Insular Surface Area and Alcohol Use Disorder. | Zhao Y et al. | β | 2019 | β |
| Comorbid HIV infection and alcohol use disorders: Converging glutamatergic and dopaminergic mechanisms underlying neurocognitive dysfunction. | Giacometti LL et al. | β | 2019 | β |
| Genetics of alcohol use disorder: a review. | Deak JD et al. | β | 2019 | β |
| Multivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol-Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort. | Meda SA et al. | β | 2019 | β |
| PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes. | Uhl GR et al. | β | 2019 | β |
| A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. | Schuckit MA | β | 2018 | β |
| Alcohol intake and periodontitis in adults aged β₯30 years: NHANES 2009-2012. | Gay IC et al. | β | 2018 | β |
| Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist. | Uhl GR et al. | β | 2018 | β |
| Cross-species molecular dissection across alcohol behavioral domains. | Farris SP et al. | β | 2018 | β |
| GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era. | Koulentaki M et al. | β | 2018 | β |
| Genome-wide meta-analysis of copy number variations with alcohol dependence. | Sulovari A et al. | β | 2018 | β |
| Metabotropic Glutamate Receptors in Alcohol Use Disorder: Physiology, Plasticity, and Promising Pharmacotherapies. | Joffe ME et al. | β | 2018 | β |
| Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders. | Colville AM et al. | β | 2018 | β |
| Role of glutamatergic system and mesocorticolimbic circuits in alcohol dependence. | Alasmari F et al. | β | 2018 | β |
| The Role of Cell Adhesion Molecule Genes Regulating Neuroplasticity in Addiction. | Muskiewicz DE et al. | β | 2018 | β |
| Alpha-1 antitrypsin inhibits RANKL-induced osteoclast formation and functions. | Akbar MA et al. | β | 2017 | β |
| Bivariate genome-wide association analyses identified genetic pleiotropic effects for bone mineral density and alcohol drinking in Caucasians. | Lu S et al. | β | 2017 | β |
| Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms. | Adkins AE et al. | β | 2017 | β |
| Alcohol words elicit reactive cognitive control in low-sensitivity drinkers. | Bailey K et al. | β | 2016 | β |
| Cadherin 13: human <i>cis</i>-regulation and selectively-altered addiction phenotypes and cerebral cortical dopamine in knockout mice. | Drgonova J et al. | β | 2016 | β |
| Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. | Bell RL et al. | β | 2016 | β |
| Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders. | Dalvie S et al. | β | 2016 | β |
| Identification of disease-associated pathways in pancreatic cancer by integrating genome-wide association study and gene expression data. | Long J et al. | β | 2016 | β |
| Test for association of common variants in GRM7 with alcohol consumption. | Melroy-Greif WE et al. | β | 2016 | β |
| Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms. | Manzardo AM et al. | β | 2015 | β |
| Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use. | Clark SL et al. | β | 2015 | β |
| Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder. | Grotewiel M et al. | β | 2015 | β |
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | Salvatore JE et al. | β | 2015 | β |
| Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence Symptoms Among Young Adults. | Long EC et al. | β | 2015 | β |
| XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans. | Juraeva D et al. | β | 2015 | β |
| A brief history of research on the genetics of alcohol and other drug use disorders. | Schuckit MA | β | 2014 | β |
| Curious cases: Altered dose-response relationships in addiction genetics. | Uhl GR et al. | β | 2014 | β |
| Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia. | Rodriguez-Murillo L et al. | β | 2014 | β |
| Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism. | Enoch MA | β | 2014 | β |
| Genetics of alcohol dependence: a review of clinical studies. | Samochowiec J et al. | β | 2014 | β |
| New glutamatergic target for alcohol and substance use disorder medications. | Vadasz C et al. | β | 2014 | β |
| Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage. | Wilhelm CJ et al. | β | 2014 | β |
| Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3Ξ±-HSD type 2 (17Ξ²-HSD type 5), moderates the subjective effects of alcohol. | Milivojevic V et al. | β | 2014 | β |
| Genome-wide association study of a quantitative disordered gambling trait. | Lind PA et al. | β | 2013 | β |
| Protein tyrosine phosphatases in health and disease. | Hendriks WJ et al. | β | 2013 | β |
| Stability of scores and correlations with drinking behaviors over 15 years for the Self-Report of the Effects of Alcohol Questionnaire. | Schuckit MA et al. | β | 2013 | β |
| The genetics of alcohol dependence. | Rietschel M et al. | β | 2013 | β |
| Viral-mediated knockdown of mGluR7 in the nucleus accumbens mediates excessive alcohol drinking and increased ethanol-elicited conditioned place preference in rats. | Bahi A | β | 2013 | β |
| An association and haplotype analysis of porcine maternal infanticide: a model for human puerperal psychosis? | Quilter CR et al. | β | 2012 | β |
| Association between in vivo alcohol metabolism and genetic variation in pathways that metabolize the carbon skeleton of ethanol and NADH reoxidation in the alcohol challenge twin study. | Lind PA et al. | β | 2012 | β |
| Convergence of genome-wide association and candidate gene studies for alcoholism. | Olfson E et al. | β | 2012 | β |
| Discovering genes involved in alcohol dependence and other alcohol responses: role of animal models. | Buck KJ et al. | β | 2012 | β |
| fMRI differences between subjects with low and high responses to alcohol during a stop signal task. | Schuckit MA et al. | β | 2012 | β |
| Genome-wide association study of comorbid depressive syndrome and alcohol dependence. | Edwards AC et al. | β | 2012 | β |
| Large scale association analysis for drug addiction: results from SNP to gene. | Guo X et al. | β | 2012 | β |
| The genetics of alcohol dependence: advancing towards systems-based approaches. | Palmer RH et al. | β | 2012 | β |
| The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 prevents reinstatement of extinguished ethanol-induced conditioned place preference in mice. | Bahi A | β | 2012 | β |
| Alcohol effects on cerebral blood flow in subjects with low and high responses to alcohol. | Tolentino NJ et al. | β | 2011 | β |
| Conversation with Marc Schuckit. | Schuckit M | β | 2011 | β |
| Genomic regions identified by overlapping clusters of nominally-positive SNPs from genome-wide studies of alcohol and illegal substance dependence. | Johnson C et al. | β | 2011 | β |
| Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies. | Joslyn G et al. | β | 2011 | β |
| mGluR7 genetics and alcohol: intersection yields clues for addiction. | Gyetvai B et al. | β | 2011 | β |
| Retracted article: Selective activation of the metabotropic glutamate receptor subtype 7 "mGluR7" attenuates acquisition, expression, and reinstatement of ethanol place preference. | Bahi A | β | 2011 | β |
| Retracted: The pre-synaptic metabotropic glutamate receptor 7 "mGluR7" is a critical modulator of ethanol sensitivity in mice. | Bahi A | β | 2011 | β |
| Variation in genes encoding the neuroactive steroid synthetic enzymes 5Ξ±-reductase type 1 and 3Ξ±-reductase type 2 is associated with alcohol dependence. | Milivojevic V et al. | β | 2011 | β |
| Analysing biological pathways in genome-wide association studies. | Wang K et al. | β | 2010 | β |