GDAP1 Is Dysregulated at DNA Methylation and H3K4me3 Levels in Alcohol Use Disorder

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1623 - 1623

Published: Feb. 14, 2025

Alcohol use disorder (AUD) contributes significantly to the global burden of disease. The susceptibility for AUD is mediated through an interaction genetic risk factors and environmental influences. These gene × environment (G E) interactions manifest as epigenetic regulations expression, among other things. Previous research suggests association between Ganglioside Induced Differentiation Associated Protein 1 (GDAP1) DNA methylation AUD. Here, we investigate dysregulation GDAP1 in comparing whole blood saliva, well H3K4-trimethylation (H3K4me3) PBMC (Peripheral Blood Mononuclear Cell) samples patients healthy control individuals. Additionally, effect abstinence-based therapy was investigated. before treatment exhibit lower promoter levels H3K4me3 near transcription start site. expression not altered. Following treatment, increased no longer differed from There significant on methylation. We conclude that epigenetically dysregulated patients, responsive at level H3K4me3. It should be investigated further establish its potential a diagnostic biomarker.

Language: Английский

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Psychiatric Genetics in Clinical Practice: Essential Knowledge for Mental Health Professionals

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The authors provide recommendations on incorporating recent advances in psychiatric genetics into clinical practice for mental health clinicians. International Society Psychiatric Genetics Education Committee met monthly to come a consensus priority topics genetics. Topics were then assigned small teams of subspecialty experts summarize the current knowledge base and create an illustrative case. included, familial aggregation, common rare genetic variants, epigenetics, gene-environment interactions, pharmacogenomics, counseling, ethical social implications. Each section was reviewed revised by all committee members finalized Chair. Key findings highlight importance understanding architecture disorders, potential applications information risk assessment, diagnosis, treatment selection, patient education, as well considerations surrounding use data. emphasizes need nuanced approach that integrates factors with environmental experiential holistic model care. As continues evolve rapidly, clinicians must stay informed about latest their Ongoing collaboration professionals, effective communication strategies are crucial harness power while avoiding pitfalls such determinism stigma. recommends balanced perspective recognizes complex interplay non-genetic shaping outcomes.

Language: Английский

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Alcohol and aging: Next‐generation epigenetic clocks predict biological age acceleration in individuals with alcohol use disorder

Alcohol Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Background Chronic heavy alcohol use is a major risk factor for premature aging and age‐related diseases. DNA methylation (DNAm)‐based epigenetic clocks are novel tools predicting biological age. However, the newest configurations, causality‐enriched clocks, have not been assessed in context of consumption disorder (AUD). Methods Epigenetic was evaluated sample 615 individuals (372 AUD patients 243 healthy controls) by applying GrimAge Version 1 (V1) 2 (V2) alongside three (CausAge, DamAge, AdaptAge). A linear model controlling diagnosis, sex, race, BMI, smoking status, five blood cell types leveraged to test associations between alcohol‐related metrics age‐adjusted clocks. Results V1 V2 maintained significant with drinking behavior measures within total both young (<40 years old) old (≥40 subgroups. Generally, slightly outperformed V1, while none demonstrated AUD. subgroup, DamAge had association number drinks. Across age subgroups, liver function enzymes, consistently sustained stronger compared V1. Among fourth‐generation exhibited gamma‐glutamyl transferase (GGT) aspartate aminotransferase subgroup; CausAge displayed GGT sample. Examining clinical biomarkers, showed improved C‐reactive protein Conclusions Overall, we observed moderately performance majority parameters tested. The lacked but demonstrate complexities inspire further research dynamics.

Language: Английский

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Human genetics and epigenetics of alcohol use disorder

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(16)

Published: Aug. 14, 2024

Alcohol use disorder (AUD) is a prominent contributor to global morbidity and mortality. Its complex etiology involves genetics, epigenetics, environmental factors. We review progress in understanding the genetics epigenetics of AUD, summarizing key findings. Advancements technology over decades have elevated research from early candidate gene studies present-day genome-wide scans, unveiling numerous genetic epigenetic risk factors for AUD. The latest GWAS on more than one million participants identified 100 variants, largest epigenome-wide association (EWAS) blood brain samples revealed tissue-specific changes. Downstream analyses enriched pathways, correlations with other traits, transcriptome-wide tissues, drug-gene interactions also discuss limitations future directions, including increasing power EWAS as well expanding diversity populations included these analyses. Larger samples, novel technologies, analytic approaches are essential; include whole-genome sequencing, multiomics, single-cell spatial transcriptomics, deep-learning prediction variant function, integrated methods disease prediction.

Language: Английский

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Is DNA methylation in the brain a mechanism of alcohol use disorder?

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Jan. 26, 2023

Alcohol use disorder (AUD) is a worldwide problem. Unfortunately, the molecular mechanisms of alcohol misuse are still poorly understood, therefore successful therapeutic approaches limited. Accumulating data indicate that tendency for compulsive inherited, suggesting genetic background as an important factor. However, probability to develop AUD also affected by life experience and environmental factors. Therefore, epigenetic modifications altered over lifetime likely contribute increased risk misuse. Here, we review literature looking link between DNA methylation in brain, common modification, AUD-related behaviors humans, mice rats. We sum up main findings, identify existing gaps our knowledge future directions research.

Language: Английский

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The pharmacotherapeutic management of comorbid bipolar disorder and alcohol use disorder

Expert Opinion on Pharmacotherapy, Journal Year: 2022, Volume and Issue: 23(10), P. 1181 - 1193

Published: May 31, 2022

Comorbidity of bipolar disorder (BD) and alcohol use (AUD) is very frequent resulting in detrimental outcomes, including increased mortality. Diagnosis AUD BD vice versa often delayed as symptoms one mimic obscure the other one. Evidence for pharmacotherapies people with comorbid remains limited, further proof-of-concept studies are urgently needed.This paper explores currently available AUD, their usefulness AUD. It also covers to some degree epidemiology, diagnosis, potential common neurobiological traits AUD.The authors conclude that more controlled needed before evidence-based guidance can be drawn up clinician's use. Since there no relevant pharmacological interactions, approved medications used safely BD. For mood stabilization, lithium should considered first adherent persons Alternatives include valproate, lamotrigine, atypical antipsychotics, partial D2/D3 receptor agonism possibly being beneficial too.

Language: Английский

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Association between Alcohol Consumption and DNA Methylation in Blood: A Systematic Review of Observational Studies

Epigenomics, Journal Year: 2022, Volume and Issue: 14(12), P. 793 - 810

Published: June 1, 2022

Aim: We systematically reviewed and evaluated current literature on alcohol consumption DNA methylation (DNAm) at the genome-wide probe-wise level in blood of adults. Materials & methods: Five databases (PubMed, Embase, Web Science, CINAHL PsycInfo) were searched until 20 December 2020. Studies assessing effect dependence DNAm not eligible. Results: 11 cross-sectional studies included with 88 to 9643 participants. Overall, all had a risk bias criteria unclear or unmet. Epigenome-wide association identified between 0 5458 differentially methylated positions, 15 observed least four studies. Conclusion: Potential markers for have been identified, but further validation large cohorts is needed.

Language: Английский

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Epigenetic Effects of Psychoactive Drugs

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 29(27), P. 2124 - 2139

Published: July 7, 2023

Abstract: Currently, and globally, we are facing the worst epidemic of psychoactive drug abuse resulting in loss hundreds thousands lives annually. Besides alcohol opioid use misuse, there has been an increase illicit psychostimulants. Epigenetics is a relatively novel area research that studies heritable alterations gene expression. Long-term administration drugs may lead to transcriptional changes brain regions related drug-seeking behaviors rewards can be passed down transgenerationally. Epigenetic biomarkers such as DNA methylation histone modifications contribute disease diagnoses. This review aims look at epigenetic brought forth by abuse.

Language: Английский

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Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: April 3, 2024

Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) identified differentially methylated genes in human peripheral brain tissue. More recently, epigenetic also evaluated hydroxymethylation hmC) the brain. However, most work postmortem tissue has examined bulk In this study, we investigated neuronal-specific 5 mC hmC alterations at CpG sites orbitofrontal cortex (OFC). Methods: Neuronal nuclei from OFC were 34 samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess genome-wide level. Differential using methylKit R package significance set false discovery rate &lt; 0.05 differential &gt; 2. Functional enrichment analyses performed, gene-level convergence an independent dataset assessed cortical Results: We 417 363 5hmC significant 59% gene promoters. Some previously implicated alcohol consumption, SYK, DNMT3A for mC, GAD1, DLX1, DLX2, GATA4 both. Convergence previous study observed 28 genes. 35 regions hmC, respectively. Lastly, GWAS analysis showed Discussion: This reveals methylome hydroxymethylome dysregulation identifying both reported potentially novel associations AUD. Our findings provide new insights into epigenomic

Language: Английский

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Dissolving Boundaries, Fostering Dependencies. the new Forensic Genetics Assemblage

Science Technology & Human Values, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

New and emerging forensic genetics technologies offer significant insight into personal information, changing the way that policing criminal justice uses of such are being considered legitimized. In this article, based on data from Central Western European countries United States America, we analyze how compounding, interdependent effects four technologies—massive parallel sequencing, epigenetics, DNA phenotyping, genetic genealogy—facilitate dissolving boundaries between medical, as well commercial non-commercial domains. Mobilizing social epistemology epistemic culture dual analytical lens, argue can witness emergence an increasingly complex assemblage, fostering dependencies agencies, research scientists, companies. At heart assemblage lies transformation central knowledge claims distinct roles responsibilities defining legitimate application information in contexts. The deepening co-dependencies within encourage increased self-governance key stakeholders, to detriment field's societal accountability legitimacy. discussion article provides a necessary starting point for reframing genetics’ governance.

Language: Английский

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