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Objective: Alcohol consumption patterns during the COVID-19 pandemic have varied notably. Participants: We examined the acute impact of the pandemic on alcohol use disorder (AUD) in a generalizable sample of college students who were surveyed pre-pandemic and re-surveyed in May 2020. Method: Items assessed pre-pandemic included DSM-5 AUD and mental health symptoms. A COVID-19 impacts questionnaire was administered, and alcohol and mental health items re-assessed. Results: AUD symptoms decreased from pre-pandemic to during the pandemic, demonstrating a change in trajectory compared to prior cohorts. Students with persistent AUD reported greater concurrent symptoms of PTSD, depression, and alcohol consumption than those with remitted AUD (ps ≤.02), but not increased COVID-19 impact. Persistent AUD status was predicted by higher sensation seeking and alcohol consumption. Conclusions: Students with concurrent mental health problems are at continued risk for persistent AUD. Findings highlight the impact of the college environment and social context for drinking on AUD. [ABSTRACT FROM AUTHOR]

Background: Variation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria. Objective: Leverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes. Methods: First, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively. Results: Three non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated. Conclusion: The proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. Materials and Methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a common, clinically and economically impactful psychiatric disorder. Genetic discovery for PTSD has accelerated at a rapid pace with nearly 100 common variants identified from genome-wide association studies (GWAS). However, large-scale studies of rare variants associated with PTSD using next-generation sequencing data have not yet been conducted. Here, we analyzed the latest whole-exome-sequencing (WES) dataset from the UK Biobank (UKB) to detect genes and gene-sets containing rare variation associated with PTSD. We conducted rare variant analyses using WES based genotypes and in 133,738 samples of European ancestry with mental health questionnaire data. PTSD phenotypes were defined from these questionnaire data. First, we used established quality-control steps for WES data. Next, synonymous, missense and loss-of-function variants were identified for analyses. We then ran SAIGE-GENE+ to generate variant and gene-level p-values for variants with a minor allele frequency (MAF) < 0.01. The GAUSS package was then used to conduct gene-set enrichment analysis for gene-level p-values. Gene-sets were selected from a wide variety of sources including the Psychiatric Genomics Consortium GWAS meta-analysis of PTSD in 2024 and curated gene-sets from studies of neuropsychiatric disorders. For variant-level analysis, there were no genome-wide significant variants detected with the most significant variant being chr1:152356894:A:G in the FLG2 gene (p = 4.98 × 10-7, MAF < 0.01). For gene-level analysis of 18,190 genes, only MAST4 was nominally significant (p = 8.2 × 10 6) for loss-of-function and missense variants. For gene-set enrichment analysis, 10 out of 189 tested gene-sets were nominally significant but not significant after multiple testing correction. Eight of these 10 gene-sets were from mouse mutants with central nervous system phenotypes with the most significant (p=0.003) being related to abnormal innervation. The remaining two gene-sets were from studies of other neuropsychiatric disorders. Finally, the gene-set from the latest PGC PTSD GWAS meta-analysis had a modest p-value of 0.089. For rare variant analysis, robustly statistically significant associations with a proxy phenotype of PTSD were not observed, even with a large sample (133k). However, nominally significant gene MAST4 has been previously associated with neurodevelopmental disorders. Similarly, some nominally enriched gene-sets were from studies of previous neuropsychiatric disorders. Notably, the gene-set from the latest common variant GWAS study had a modest p-value in this analysis. Future studies which focus on understanding the overlapping information of these types of variants can shed additional light on the genetic architecture of PTSD. Our future extensions of these analyses will include integrative analytic approaches and importantly expand to multiple ancestry samples across several biobanks in order to advance the understanding of PTSD. This study was conducted using the UK Biobank Resource application number 30782. [ABSTRACT FROM AUTHOR]