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The Molecular Basis of Alcohol Use Disorder (AUD). Genetics, Epigenetics, and Nutrition in AUD: An Amazing Triangle.

ABSTRACT: Alcohol use disorder (AUD) is a very common and complex disease, as alcohol is the most widely used addictive drug in the world. This disorder has an enormous impact on public health and social and private life, and it generates a huge number of social costs. Alcohol use stimulates hypothalamic-pituitary-adrenal (HPA) axis responses and is the cause of many physical and social problems (especially liver disease and cancer), accidental injury, and risky sexual behavior. For years, researchers have been trying to identify the genetic basis of alcohol use disorder, the molecular mechanisms responsible for its development, and an effective form of therapy. Genetic and environmental factors are known to contribute to the development of AUD, and the expression of genes is a complicated process that depends on epigenetic modulations. Dietary nutrients, such as vitamins, may serve as one these modulators, as they have a direct impact on epigenomes. In this review, we connect gathered knowledge from three emerging fields-genetics, epigenetics, and nutrition-to form an amazing triangle relating to alcohol use disorder.

SUBMITTER: Siomek-Gorecka A

PROVIDER: S-EPMC8072802 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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The Molecular Basis of Alcohol Use Disorder (AUD). Genetics, Epigenetics, and Nutrition in AUD: An Amazing Triangle.

Siomek-Gorecka Agnieszka A Dlugosz Anna A Czarnecki Damian D

International journal of molecular sciences 20210420 8

Alcohol use disorder (AUD) is a very common and complex disease, as alcohol is the most widely used addictive drug in the world. This disorder has an enormous impact on public health and social and private life, and it generates a huge number of social costs. Alcohol use stimulates hypothalamic-pituitary-adrenal (HPA) axis responses and is the cause of many physical and social problems (especially liver disease and cancer), accidental injury, and risky sexual behavior. For years, researchers hav ...[more]

PMID: 33924016

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Project description:BackgroundAlcohol use disorder (AUD) causes significant morbidity, mortality, and injuries. According to reports, approximately 5% of all registered deaths in Denmark could be due to AUD. The problem is compounded by the late identification of patients with AUD, a situation that can cause enormous problems, from psychological to physical to economic problems. Many individuals suffering from AUD never undergo specialist treatment during their addiction due to obstacles such as taboo and the poor performance of current screening tools. Therefore, there is a lack of rapid intervention. This can be mitigated by the early detection of patients with AUD. A clinical decision support system (DSS) powered by machine learning (ML) methods can be used to diagnose patients' AUD status earlier.MethodsThis study proposes an effective AUD prediction model (AUDPM), which can be used in a DSS. The proposed model consists of four distinct components: (1) imputation to address missing values using the k-nearest neighbours approach, (2) recursive feature elimination with cross validation to select the most relevant subset of features, (3) a hybrid synthetic minority oversampling technique-edited nearest neighbour approach to remove noise and balance the distribution of the training data, and (4) an ML model for the early detection of patients with AUD. Two data sources, including a questionnaire and electronic health records of 2571 patients, were collected from Odense University Hospital in the Region of Southern Denmark for the AUD-Dataset. Then, the AUD-Dataset was used to build ML models. The results of different ML models, such as support vector machine, K-nearest neighbour, decision tree, random forest, and extreme gradient boosting, were compared. Finally, a combination of all these models in an ensemble learning approach was selected for the AUDPM.ResultsThe results revealed that the proposed ensemble AUDPM outperformed other single models and our previous study results, achieving 0.96, 0.94, 0.95, and 0.97 precision, recall, F1-score, and accuracy, respectively. In addition, we designed and developed an AUD-DSS prototype.ConclusionIt was shown that our proposed AUDPM achieved high classification performance. In addition, we identified clinical factors related to the early detection of patients with AUD. The designed AUD-DSS is intended to be integrated into the existing Danish health care system to provide novel information to clinical staff if a patient shows signs of harmful alcohol use; in other words, it gives staff a good reason for having a conversation with patients for whom a conversation is relevant.

Project description:AimsAlcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article.MethodsIn this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS).ResultsSeveral potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown.ConclusionsAlthough studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD.Short summaryThis review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH.

Project description:BackgroundFollowing a finding of alcohol use among children aged 5-8 years old in Mbale, Uganda, this project investigates the magnitude of alcohol and substance use among children ged 6-13 years old and related household, community, school, health system and clinical factors.MethodsThe project includes four larger work packages (WPs). WP1 comprises management, WP2 and 3 include the scientific components and WP4 includes integration of results, dissemination, policy and implementation advice. This protocol presents the planned research work in WP 2 and 3. WP2 comprises the adaptation and validation of the alcohol use screening tool Car-Relax-Alone-Forget-Family and Friends-Trouble (CRAFFT) to the age group and setting. WP3 comprises four substudies (SS). SS1 is a cross-sectional community household survey with an estimated sample size of 3500 children aged 6-13 years and their caregivers. We apply cluster sampling and systematic sampling within the clusters. Data collection includes a structured questionnaire for caregiver and child, measuring social and demographic factors, mental health status, alcohol and substance use, nutrition history and anthropometry. Urine samples from children will be collected to measure ethyl glucuronide (EtG), a biological marker of alcohol intake. Further, facilitators, barriers and response mechanisms in the health system (SS2) and the school system (SS3) is explored with surveys and qualitative assessments. SS4 includes qualitative interviews with children. Analysis will apply descriptive statistics for the primary outcome of establishing the magnitude of alcohol drinking and substance use, and associated factors will be assessed using appropriate regression models. The substudies will be analysed independently, as well as inform each other through mixed methods strategies at the stages of design, analysis, and dissemination.Ethics and disseminationData protection and ethical approvals have been obtained in Uganda and Norway, and referral procedures developed. Dissemination comprises peer-reviewed, open access research papers, policy recommendations and intersectoral dialogues.Trial registration numberClinicaltrials.gov 29.10.2020 (NCT04743024).

Dataset Information

The Molecular Basis of Alcohol Use Disorder (AUD). Genetics, Epigenetics, and Nutrition in AUD: An Amazing Triangle.

Publications

The Molecular Basis of Alcohol Use Disorder (AUD). Genetics, Epigenetics, and Nutrition in AUD: An Amazing Triangle.

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