Epigenetics of alcohol use disorder-A review of recent advances in DNA methylation profiling.

Alcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there is a heritable component, the etiology of AUD is complex and can involve environmental exposures like trauma and can be associated with many different patterns of alcohol consumption. Epigenetic modifications, which can mediate the influence of genetic variants and environmental variables on gene expression, have emerged as an important area of AUD research.

Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation.

Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD.

Lipid profile dysregulation predicts alcohol withdrawal symptom severity in individuals with alcohol use disorder.

Alcohol withdrawal syndrome (AWS) is a serious medical condition of high variability in alcohol use disorder (AUD) after drinking cessation. Identification of clinical biomarkers capable of detecting severe AWS is needed. While alcohol consumption and withdrawal are linked with lipid profile dysregulation, the relationship between lipid levels (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) and AWS is unknown.

Adverse Childhood Experiences are Associated with High-Intensity Binge Drinking Behavior in Adulthood and Mediated by Psychiatric Disorders.

Aim: High-intensity binge drinking (HIBD), defined as two or more times the gender-specific binge threshold, is rapidly increasing in the USA; however, the underlying contributing factors are poorly understood. This study investigated the relationship of adverse childhood experiences (ACEs) and HIBD.

Methods: Two independent, cross-sectional samples were analysed: (a) past 12-month drinkers in the National Epidemiological Survey on Alcohol and Related Conditions-III (NESARC-III; n = 25,552) and (b) the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample (n = 1303).

Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2.

To investigate the potential role of alcohol use disorder (AUD) in aging processes, we employed Levine's epigenetic clock (DNAm PhenoAge) to estimate DNA methylation age in 331 individuals with AUD and 201 healthy controls (HC). We evaluated the effects of heavy, chronic alcohol consumption on epigenetic age acceleration (EAA) using clinical biomarkers, including liver function test enzymes (LFTs) and clinical measures. To characterize potential underlying genetic variation contributing to EAA in AUD, we performed genome-wide association studies (GWAS) on EAA, including pathway analyses.

Association of High-Intensity Binge Drinking With Lipid and Liver Function Enzyme Levels.

Importance: The prevalence of high-intensity binge drinking (HIBD), defined as consuming 2 or more times the binge threshold defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is rapidly increasing in the United States. While the relationship between alcohol consumption and lipid and liver function enzyme (LFT) biomarkers has been previously examined, the associations of HIBD with those biomarkers remain unknown.

Objective: To examine associations of HIBD with lipid and LFT levels in a cross-sectional sample enriched with participants who engage in HIBD.

PCSK9 is Increased in Cerebrospinal Fluid of Individuals With Alcohol Use Disorder.

Background: Recent studies have shown that alcohol use affects the regulation and expression of proprotein convertase subtilisin/kexin 9 (PCSK9). While a major role of PCSK9 in hepatic function and lipid regulation has been clearly established, other pleiotropic effects remain poorly understood. Existing research suggests a positive association between PCSK9 expression in the brain and psychopathology, with increased levels of PCSK9 in the cerebrospinal fluid (CSF) of individuals with dementia and epigenetic modifications of PCSK9 associated with alcohol use disorder (AUD).