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. We followed up on relevant top findings with in silico expression quantitative trait loci (eQTL) analyses for biological function using the BRAINEAC database. There was a 2.22-year age acceleration in AUD compared to controls after adjusting for gender and blood cell composition (p = 1.85 × 10 −5). This association remained significant after adjusting for race, body mass index, and smoking status (1.38 years, p = 0.02). Secondary analyses showed more pronounced EAA in individuals with more severe AUD-associated phenotypes, including elevated gammaglutamyl transferase (GGT) and alanine aminotransferase (ALT), and higher number of heavy drinking days (all ps < 0.05). The genome-wide meta-analysis of EAA in AUD revealed a significant single nucleotide polymorphism (SNP), rs916264 (p = 5.43 × 10 −8), in apolipoprotein L2 (APOL2) at the genome-wide level. The minor allele A of rs916264 was associated with EAA and with increased mRNA expression in hippocampus (p = 0.0015). Our data demonstrate EAA in AUD and suggest that disease severity further accelerates epigenetic aging. EAA was associated with genetic variation in APOL2, suggesting potential novel biological mechanisms for age acceleration in AUD.

Key Points Question What changes in circulating lipid and liver function enzyme levels are associated with high-intensity binge drinking? Findings In this cross-sectional study of 1519 participants, high-intensity binge drinking was associated with increased cholesterol, triglyceride, and liver function enzyme levels. Meaning Lipid and liver function enzyme levels demonstrate dose-dependent increases with high-intensity binge drinking, indicating potential adverse health outcomes may be associated with such drinking behavior.

Stigma towards people with mental illness is a worldwide concern. A five-nation survey of medical student attitudes towards people with mental illness recently reported far lower levels of social acceptance among Chinese medical students compared to those from the US, Brazil, Ghana, and Nigeria. This qualitative study presented recent Chinese medical school graduates with probes based on questions used in the aforementioned cross-national study to elicit their views of factors underlying the negative attitudes towards social acceptance of people with mental illness. One-hour interviews were conducted with twenty psychiatry residents in June, 2016. Of 241 coded responses concerning negative attitudes, 51.5% were coded as reflecting fear of violent behavior, 22.8% as loss of face (i.e. shame from interpersonal associations), 17.0% lowered social status, 4.98% nonconforming social behavior, and 3.73% the heritability of mental illness. Low levels of social acceptance of individuals with mental illness among medical students in China are largely related to fears of violence of and loss of face. Understanding the attitudes of medical students may inform efforts to reduce stigma through educational initiatives targeted at both medical students and the general public.