Endophenotypes for Alcohol Use Disorder: An Update on the Field.
- Authors
- Salvatore, Jessica E; Gottesman, Irving I; Dick, Danielle M
- Year
- 2015
- Journal
- Current addiction reports
- PMID
- 26236574
- DOI
- 10.1007/s40429-015-0046-y
- PMCID
- PMC4520241
The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches to AUD endophenotypes have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically-influenced pathways toward AUD.
Depiction of the interplay among genetic and environmental factors that contribute to liability for alcohol use disorder (AUD), and the contribution of candidate endophenotypes and their associated genes and gene regions. Genes and gene regions that are associated with AUD candidate endophenotypes are highlighted here (references are documented in Table 2). These should be considered illustrative and not exhaustive. The “reaction surface” represents the probabilistic interplay among genetic and environmental factors in the development of risky alcohol use (i.e., consuming alcohol in quantities that put individuals at risk for alcohol-related harms) and AUD. Figure adapted from Gottesman & Gould [3] and used with permission.
LLM interpretation
This conceptual diagram illustrates the interplay between genetic and environmental factors in the development of alcohol use disorder (AUD). The bottom section maps specific candidate genes and genomic regions to various candidate endophenotypes, such as executive functions and EEG variables. These factors feed into a "reaction surface" plot, which visualizes how the liability for risky alcohol use and AUD evolves across age (from -9 months to 30 years) relative to environmental influences.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Revisiting drunk driving risk among individuals with alcohol use disorder using unsupervised learning: From clinical characteristics and neuropsychological performance to EEG data. | Su YR et al. | — | 2026 | → |
| Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample. | Moe JS et al. | — | 2025 | → |
| Chronic alcohol-induced brain states limit propagation of direct cortical stimulation. | Habelt B et al. | — | 2025 | → |
| Examining social attention as a predictor of problem drinking behavior: A longitudinal study using eye-tracking. | Han J et al. | — | 2025 | → |
| Sex and Genetic Differences in Behavioral Engagement of Crossed High Alcohol-Preferring and Low Alcohol-Preferring Mice. | Starski P et al. | — | 2025 | → |
| The Effects of Alcohol in Groups of Heavy Drinking Young Adults: A Multi-Modal Investigation of Alcohol Responses in a Laboratory Social Setting. | Creswell KG et al. | — | 2025 | → |
| Cognitive impairment in 'non-user' first-degree relatives of persons with cannabis dependence syndrome: A pilot, endophenotype study. | Das S et al. | — | 2024 | → |
| Genetic influences on alcohol sensitivity: A critical review. | Yeung EW et al. | — | 2024 | → |
| Neural responses to reward, threat, and emotion regulation and transition to hazardous alcohol use. | Kirk-Provencher KT et al. | — | 2024 | → |
| Sweet liking predicts liking and familiarity of some alcoholic beverages, but not alcohol intake: A population study using a split-sample approach. | Spinelli S et al. | — | 2024 | → |
| Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models. | Bhandari A et al. | — | 2024 | → |
| Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. | Popova D et al. | — | 2023 | → |
| Shared genetic liability for alcohol consumption, alcohol problems, and suicide attempt: Evaluating the role of impulsivity. | Stephenson M et al. | — | 2023 | → |
| The collaborative study on the genetics of alcoholism: Brain function. | Meyers JL et al. | — | 2023 | → |
| Association of Alcohol Use Disorder Risk With <i>ADH1B, DRD2, FAAH, SLC39A8, GCKR</i>, and <i>PDYN</i> Genetic Polymorphisms. | Legaki E et al. | — | 2022 | → |
| Exploration of the Impact of Combining Risk Phenotypes on the Likelihood of Alcohol Problems in Young Adults. | Kampov-Polevoy A et al. | — | 2022 | → |
| Identifying alcohol misuse biotypes from neural connectivity markers and concurrent genetic associations. | Zhu T et al. | — | 2022 | → |
| Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder. | Denham AN et al. | — | 2022 | → |
| Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder. | Park CI et al. | — | 2021 | → |
| Parietal P3 and midfrontal theta prospectively predict the development of adolescent alcohol use. | Harper J et al. | — | 2021 | → |
| Prediction of ethanol self-administration in pre-weanling, adolescent, and young adult rats. | Soledad Fernández M et al. | — | 2021 | → |
| Prospective Associations between Attitudes toward Sweet Foods, Sugar Consumption, and Cravings for Alcohol and Sweets in Early Recovery from Alcohol Use Disorders. | Braun TD et al. | — | 2021 | → |
| The Association Between Impulsivity and Relapse in Patients With Alcohol Use Disorder: A Literature Review. | Sliedrecht W et al. | — | 2021 | → |
| The Etiologic, Theory-Based, Ontogenetic Hierarchical Framework of Alcohol Use Disorder: A Translational Systematic Review of Reviews. | Boness CL et al. | — | 2021 | → |
| Translational opportunities in animal and human models to study alcohol use disorder. | Nieto SJ et al. | — | 2021 | → |
| Association of PPM1G methylation with risk-taking in alcohol use disorder. | Park CI et al. | — | 2020 | → |
| Cortisol as a Biomarker of Alcohol Use in Combat Veterans: A Literature Review and Framework for Future Research. | Szabo YZ et al. | — | 2020 | → |
| Different aspects of impulsivity in chronic alcohol use disorder with and without comorbid problem gambling. | Kovács I et al. | — | 2020 | → |
| Alcohol Withdrawal and Proopiomelanocortin Neuropeptides in an Animal Model of Alcohol Dependence. | Müschen LH et al. | — | 2019 | → |
| Decreased event-related theta power and phase-synchrony in young binge drinkers during target detection: An anatomically-constrained MEG approach. | Correas A et al. | — | 2019 | → |
| Genetic Epidemiology of Liability for Alcohol-Induced Blacking and Passing Out. | Davis CN et al. | — | 2019 | → |
| Interactive Effects of Naturalistic Drinking Context and Alcohol Sensitivity on Neural Alcohol Cue-Reactivity Responses. | Martins JS et al. | — | 2019 | → |
| Molecular tools to elucidate factors regulating alcohol use. | Logrip ML | — | 2019 | → |
| Neural oscillatory dynamics of inhibitory control in young adult binge drinkers. | Holcomb LA et al. | — | 2019 | → |
| Pharmacogenetics of alcohol use disorder treatments: an update. | Hartwell EE et al. | — | 2019 | → |
| Target-related parietal P3 and medial frontal theta index the genetic risk for problematic substance use. | Harper J et al. | — | 2019 | → |
| Ethanol Regulates Presynaptic Activity and Sedation through Presynaptic Unc13 Proteins in <i>Drosophila</i>. | Xu S et al. | — | 2018 | → |
| The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption. | Sloan ME et al. | — | 2018 | → |
| Trait Impulsivity in Alcohol-naïve Offspring at High Risk for Alcoholism. | Kumar R et al. | — | 2018 | → |
| A prospective study of genetic factors, human laboratory phenotypes, and heavy drinking in late adolescence. | Hendershot CS et al. | — | 2017 | → |
| A Review of Developmental Considerations in Human Laboratory Alcohol Research. | Hendershot CS et al. | — | 2017 | → |
| Disrupted resting brain graph measures in individuals at high risk for alcoholism. | Holla B et al. | — | 2017 | → |
| Endophenotype best practices. | Iacono WG et al. | — | 2017 | → |
| Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers. | Weerts EM et al. | — | 2017 | → |
| Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study. | Li JJ et al. | — | 2017 | → |
| Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research. | Bujarski S et al. | — | 2016 | → |
| Heightened Impulsivity: Associated with Family History of Alcohol Misuse, and a Consequence of Alcohol Intake. | Sanchez-Roige S et al. | — | 2016 | → |