ArticleAlcoholism, clinical and experimental research2017
Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.
Article in Alcoholism, clinical and experimental research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
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- Modeling Brain Gene Expression in Alcohol Use Disorder with Genetic Animal Models.Current topics in behavioral neurosciences · 2025Review
- Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models.International journal of molecular sciences · 2024Review
- Nicotine Motivated Behavior inInternational journal of molecular sciences · 2024Article
- Contagious Transmission in a Swedish National Sample of Alcohol Use Disorders as a Function of Geographical Proximity Among Siblings and Propinquity-of-Rearing Defined Acquaintances.Journal of studies on alcohol and drugs · 2023Article
- Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder.International journal of biological sciences · 2023Review
- Adolescent binge ethanol impacts H3K36me3 regulation of synaptic genes.Frontiers in molecular neuroscience · 2023Article
- Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder.Non-coding RNA · 2022Review
- mRNA and long non-coding RNA expression profiles of rotator cuff tear patients reveal inflammatory features in long head of biceps tendon.BMC medical genomics · 2022Article
- GeneCup: mining PubMed and GWAS catalog for gene-keyword relationships.G3 (Bethesda, Md.) · 2022Article
- Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use.Alcoholism, clinical and experimental research · 2021Article
- Transcriptional analysis of the response of C. elegans to ethanol exposure.Scientific reports · 2021Article
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
- On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption.Frontiers in psychiatry · 2021Review
- Epigenetic and non-coding regulation of alcohol abuse and addiction.International review of neurobiology · 2021Article
- ERR and dPECR Suggest a Link Between Neuroprotection and the Regulation of Ethanol Consumption Preference.Frontiers in psychiatry · 2021Article
- Assessing the Role of Long Noncoding RNA in Nucleus Accumbens in Subjects With Alcohol Dependence.Alcoholism, clinical and experimental research · 2020Article
- Flying Together:International journal of molecular sciences · 2020Review
- Within-Family Transmission of Alcohol Use Disorder in Parent-Offspring, Sibling, and Cousin Pairs: A Contagion Model.The Journal of nervous and mental disease · 2020Article
Corrections and comments
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Authors and funding
57 authors at 16 institutions in 6 countries.
Funding
Abstract
backgroundAlcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified.
methodsWe conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue.
resultsWe detected significant association in COL6A3 and suggestive association in 2 previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in Caenorhabditis elegans reduced EtOH sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance (AFT). Klf12 expression correlated with locomotor activation following EtOH injection in mice. Loss of function of the RYR3 ortholog reduced EtOH sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer EtOH in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens (NAc).
conclusionsWe detect association between AD and COL6A3, KLF12, RYR3, and LOC339975. Despite nonreplication of COL6A3, KLF12, and RYR3 signals, orthologs of these genes influence behavioral response to EtOH in MOs, suggesting potential involvement in human EtOH response and AD liability. The associated LOC339975 allele may influence gene expression in human NAc. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders.
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