A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity.
paper
Primary
Public
- Authors
- Schuckit, Marc A
- Year
- 2018
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 29623680
- DOI
- 10.1111/acer.13628
- PMCID
- PMC5916326
Attributes of alcohol sensitivity are present before alcohol use disorders (AUDs) develop, they predict those adverse alcohol outcomes, are familial in nature, and many are heritable. Whether measured by alcohol challenges or retrospective reports of numbers of drinks required for effects, alcohol sensitivity reflects multiple phenotypes, including low levels of alcohol response and alcohol-related stimulation. Identification of genes that contribute to alcohol sensitivity could help identify individuals carrying risks for AUDs through their alcohol responses for whom early intervention might mitigate their vulnerability. Such genes could also improve understanding of biological underpinnings of AUDs, which could lead to new treatment approaches. However, the existing literature points to a wide range of genetic mechanisms that might contribute to alcohol responses, and few such genetic findings have been widely replicated. This critical review describes the potential impact of the diverse methods used to study sensitivity on the diversity of genetic findings that have been reported, places the genetic variants mentioned in the literature into broader categories rather than isolated results, and offers suggestions regarding how to advance the field by interpreting findings in light of the methods used to select research subjects and to measure alcohol sensitivity. To date, the most promising results have been for GABA, glutamate, opioid, dopamine, serotonin, and cholinergic system genes. The more gene variants that can be identified as contributors to sensitivity the better future gene screening platforms or polygenic scores are likely to be.
Description of Potential Pathways Across Studies Working to Identify Genes Related to Alcohol Sensitivity
| # | Section | Preview |
|---|---|---|
| 0 | Introduction | Predicting the development of complex genetically influenced disorders is complicated. Each… |
| 1 | Introduction | Alcohol challenges have identified multiple characteristics that contribute to a person’s… |
| 2 | Introduction | The low LR, or low sensitivity, focuses more on depressant effects of alcohol, but extends beyond… |
| 3 | Introduction | This paper reviews the current state of the search for genes that contribute to alcohol sensitivity.… |
| 4 | A brief review of major methods used to evaluate alcohol reaction phenotypes | As demonstrated in Figure 1, across studies evaluations of alcohol sensitivity can flow from alcohol… |
| 5 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | Our group focuses on identifying genetically-influenced characteristics that predict future binge… |
| 6 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | A different oral alcohol paradigm that focuses on predicting future alcohol-related problems in… |
| 7 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | Other alcohol paradigms infuse IV alcohol at constant rates to reach peak BACs in ~20 minutes, and… |
| 8 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | Alcohol sensitivity can also be measured by retrospective questionnaires that record usual numbers… |
| 9 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | SRE and alcohol oral single dose challenge-based low LRs predict heavy drinking up to 35 years later… |
| 10 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Examples of measures of alcohol reactions across different populations | SRE scores have validities and retest reliabilities of .70 to .80 or higher (Kalu et al., 2008; Ray… |
| 11 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR | The emphasis in studies of low LR is on predicting onsets of heavy drinking and multiple alcohol… |
| 12 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR | The major source of prospective data on low LR comes from the 35-year-long San Diego Prospective… |
| 13 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR | Beginning in 1988, 99% of the probands from the SDPS were followed up at about age 30, when the low… |
| 14 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR — High stimulation with alcohol | Studies of high stimulation effects of alcohol often begin with non-alcohol dependent heavy drinkers… |
| 15 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR — High stimulation with alcohol | The primary source of these data involved 190 subjects who consumed oral alcohol during two… |
| 16 | A brief review of major methods used to evaluate alcohol reaction phenotypes — Two relevant LR phenotypes — Low LR — High stimulation with alcohol | Studies documenting alcohol-related low LR and/or high stimulation are the focus of this review of… |
| 17 | The search for gene variants related to alcohol sensitivity (See Table 1) | While no receptors are dedicated specifically to alcohol, this drug has prominent effects on gamma… |
| 18 | The search for gene variants related to alcohol sensitivity (See Table 1) | The following material reviews gene variants that might relate to alcohol sensitivity and are worth… |
| 19 | The search for gene variants related to alcohol sensitivity (See Table 1) — Alcohol metabolizing enzymes | Variants of the genes for ALDH2 on chromosome 12q24.12 (e.g., rs671), ADH1B on chromosome 4q23… |
1–20 of 58
Next →
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| The 10-year stability of three subscale scores of the Self-Report of the Effects of Alcohol measure and their relationship to changes in drinking quantities over the same period. | Schuckit MA 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 | → |
| Body Mass Index Is Inversely Associated With Level of Response to Alcohol: Role of Total Body Water. | Vergeer RR et al. | — | 2025 | → |
| Inhibitory control in the sober state as a function of alcohol sensitivity: a pilot functional magnetic resonance imaging (fMRI) study. | Cofresí RU et al. | — | 2025 | → |
| Genetic influences on alcohol sensitivity: A critical review. | Yeung EW et al. | — | 2024 | → |
| Mesocorticolimbic system reactivity to alcohol use-related visual cues as a function of alcohol sensitivity phenotype: A pilot fMRI study. | Cofresí RU et al. | — | 2024 | → |
| Retrospective self-reports of sensitivity to the effects of alcohol: Trait-like stability and concomitant changes with alcohol involvement. | Kohen CB et al. | — | 2024 | → |
| The PDE4 inhibitor apremilast modulates ethanol responses in Gabrb1-S409A knock-in mice via PKA-dependent and independent mechanisms. | Blednov YA et al. | — | 2024 | → |
| A multicomponent ethanol response battery across a cumulative dose ethanol challenge reveals diminished adolescent rat ethanol responsivity relative to adults. | Vetreno RP et al. | — | 2023 | → |
| Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. | Mulholland PJ et al. | — | 2023 | → |
| Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking. | Juanes RC et al. | — | 2023 | — |
| Do personality characteristics predict future alcohol problems after considering current demography, substance use, and alcohol response? | Schuckit MA et al. | — | 2023 | → |
| G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice. | Wei S et al. | — | 2023 | → |
| Natural allelic variation modifies acute ethanol response phenotypes in wild strains of C. elegans. | van Wijk MH et al. | — | 2023 | → |
| Self-report assessment of alcohol sensitivity: An examination of the effects of different probes. | Boness CL et al. | — | 2023 | → |
| The Promise of an Evolutionary Perspective of Alcohol Consumption. | Clites BL et al. | — | 2023 | → |
| Applying network analysis to investigate substance use symptoms associated with drug overdose. | Ingram PF et al. | — | 2022 | → |
| AUD Risk, Diagnoses, and Course in a Prospective Study Across Two Generations: Implications for Prevention. | Schuckit MA | — | 2022 | → |
| FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION. | Bowen MT et al. | — | 2022 | → |
| GABA<sub>A</sub> subunit single nucleotide polymorphisms show sex-specific association to alcohol consumption and mental distress in a Norwegian population-based sample. | Moe JS et al. | — | 2022 | → |
| Hazardous drinking and alcohol use disorders. | MacKillop J et al. | — | 2022 | → |
| Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli. | McKenna BS et al. | — | 2022 | → |
| Moderators of subjective response to alcohol in the human laboratory. | Nieto SJ et al. | — | 2022 | → |
| Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele. | Chen YC et al. | — | 2021 | → |
| Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers. | Rodriguez FD et al. | — | 2021 | → |
| Combined and sequential effects of alcohol and methamphetamine in animal models. | Stafford AM et al. | — | 2021 | → |
| Cross-sectional and prospective associations of drinking characteristics with scores from the Self-Report of the Effects of Alcohol questionnaire and findings from alcohol challenges. | Schuckit MA et al. | — | 2021 | → |
| Deletion of Tlr3 reduces acute tolerance to alcohol and alcohol consumption in the intermittent access procedure in male mice. | Blednov YA et al. | — | 2021 | → |
| Relationship between level of response to alcohol and acute tolerance. | Anthenelli RM et al. | — | 2021 | → |
| The <i>foraging</i> gene affects alcohol sensitivity, metabolism and memory in <i>Drosophila</i>. | Oepen AS et al. | — | 2021 | → |
| Tolerance to alcohol: A critical yet understudied factor in alcohol addiction. | Elvig SK et al. | — | 2021 | → |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
| Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study. | Acevedo MB et al. | — | 2020 | → |
| Characteristics associated with denial of problem drinking among two generations of individuals with alcohol use disorders. | Schuckit MA et al. | — | 2020 | → |
| Genome-wide association studies of the self-rating of effects of ethanol (SRE). | Lai D et al. | — | 2020 | → |
| Individual differences in biological regulation: Predicting vulnerability to drug addiction, obesity, and other dysregulatory disorders. | Ramsay DS et al. | — | 2020 | → |
| On the path towards personalized medicine: Implications of pharmacogenetic studies of alcohol use disorder medications. | Nieto SJ et al. | — | 2020 | → |
| Subjective Effects of Alcohol Predict Alcohol Choice in Social Drinkers. | Li J et al. | — | 2020 | → |
| SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol. | Mathies LD et al. | — | 2020 | → |
| The Search for Contributors to Low Rates of Recognition of Paternal Alcohol Use Disorders in Offspring From the San Diego Prospective Study. | Schuckit MA et al. | — | 2020 | → |
| Interactive Effects of Naturalistic Drinking Context and Alcohol Sensitivity on Neural Alcohol Cue-Reactivity Responses. | Martins JS et al. | — | 2019 | → |
| Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents. | Edwards AC et al. | — | 2019 | → |
| Performance of the Self-Report of the Effects of Alcohol Questionnaire Across Sexes and Generations. | Schuckit MA et al. | — | 2019 | → |
| Predictors of Increases in Alcohol Problems and Alcohol Use Disorders in Offspring in the San Diego Prospective Study. | Schuckit MA et al. | — | 2019 | → |
| The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample. | Johnson EC et al. | — | 2019 | → |
| A 22-Year Follow-Up (Range 16 to 23) of Original Subjects with Baseline Alcohol Use Disorders from the Collaborative Study on Genetics of Alcoholism. | Schuckit MA et al. | — | 2018 | → |
| Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. | Edwards AC et al. | — | 2018 | → |