Does Drinking Location Matter? Profiles of Risky Single-Occasion Drinking by Location and Alcohol-Related Harm among Young Men.

In adolescents and young adults, acute consequences like injuries account for a substantial proportion of alcohol-related harm, especially in risky single-occasion (RSO) drinkers. The primary aim of the study was to characterize different drinking profiles in RSO drinkers according to drinking locations and their relationship to negative, alcohol-related consequences. The sample consisted of 2746 young men from the Cohort Study on Substance Use Risk Factors who had reported drinking six or more drinks on a single-occasion at least monthly over the preceding 12 months. Principal component analysis on the frequency and amount of drinking at 11 different locations was conducted, and 2 distinguishable components emerged: a non-party-dimension (loading high on theater/cinema, sport clubs, other clubs/societies, restaurants, and sport events) and a party-dimension (loading high on someone else's home, pubs/bars, discos/nightclubs, outdoor public places, special events, and home). Differential impacts of drinking location profiles were observed on severe negative alcohol-related consequences (SAC). Relative to those classified as low or intermediate in both dimensions, no significant difference experiencing SAC was found among those who were classified as high in the non-party-dimension only. However, those who were classified as high in the party-dimension alone or in both dimensions were more likely to experience SAC. These differential effects remained after adjusting for alcohol consumption (volume and risky single-occasion drinking), personality traits, and peer-influence [adjusted OR = 0.83 (0.68-1.02), 1.57 (1.27-1.96), and 1.72 (1.23-2.41), respectively], indicating independent effects of drinking location on SAC. The inclusion of sociodemographic factors did not alter this association. The fact that this cluster of party-dimension locations seems to predispose young men to experiencing SAC has important implications for alcohol control policies

An analysis of genetically regulated gene expression across multiple tissues implicates novel gene candidates in Alzheimer's disease

Introduction: Genome-wide association studies (GWAS) have successfully identified multiple independent genetic loci that harbour variants associated with Alzheimer's disease, but the exact causal genes and biological pathways are largely unknown. Methods: To prioritise likely causal genes associated with Alzheimer's disease, we used S-PrediXcan to integrate expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression (GTEx) study and CommonMind Consortium (CMC) with Alzheimer's disease GWAS summary statistics. We meta-analysed the GTEx results using S-MultiXcan, prioritised disease-implicated loci using a computational fine-mapping approach, and performed a biological pathway analysis on the gene-based results. Results: We identified 126 tissue-specific gene-based associations across 48 GTEx tissues, targeting 50 unique genes. Meta-analysis of the tissue-specific associations identified 73 genes whose expression was associated with Alzheimer's disease. Additional analyses in the dorsolateral prefrontal cortex from the CMC identified 12 significant associations, 8 of which also had a significant association in GTEx tissues. Fine-mapping of causal gene sets prioritised gene candidates in 10 Alzheimer's disease loci with strong evidence for causality. Biological pathway analyses of the meta-analysed GTEx data and CMC data identified a significant enrichment of Alzheimer's disease association signals in plasma lipoprotein clearance, in addition to multiple immune-related pathways. Conclusions: Gene expression data from brain and peripheral tissues can improve power to detect regulatory variation underlying Alzheimer's disease. However, the associations in peripheral tissues may reflect tissue-shared regulatory variation for a gene. Therefore, future functional studies should be performed to validate the biological meaning of these associations and whether they represent new pathogenic tissues