GSCAN GWAS Meta-analysis of Tobacco and Alcohol use
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PROVIDER: PRJNA532238 | ENA |
REPOSITORIES: ENA
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Project description:GSCAN GWAS Meta-analysis of Tobacco and Alcohol use
| PRJNA532239 | ENA
Project description:We employed high-throughput gene expression profiling to understand gene expression differences between habits-associated tongue cancers and non-habits tongue cancers. Expression data from 22 tumors were used to identify a set of 18 differentially expressed genes that can, with high precision, distinguish the two etiologically diverse oral tumors. Results from the study provide insights into molecular carcinogenesis of tongue cancers without a history of tobacco and alcohol use.
2013-11-05 | GSE42023 | GEO
Project description:We employed high-throughput gene expression profiling to understand gene expression differences between habits-associated tongue cancers and non-habits tongue cancers. Expression data from 22 tumors were used to identify a set of 18 differentially expressed genes that can, with high precision, distinguish the two etiologically diverse oral tumors. Results from the study provide insights into molecular carcinogenesis of tongue cancers without a history of tobacco and alcohol use. We used RNA from 22 samples that included 10 tumor biopsies from habits-associated cancers and 12 from non-habits associated cancers.
2013-11-05 | E-GEOD-42023 | biostudies-arrayexpress
Project description:<p>The Australian twin-family study of alcohol use disorder (OZALC study) derives from telephone diagnostic interview studies of two general population volunteer cohorts of Australian twins (cohort 1, mostly born 1940-1964; cohort 2, born 1964-71) and the spouses of the former cohort - a total of over 11,000 families. Three coordinated studies, using a shared assessment protocol and with a shared goal of gene-discovery, were conducted - one funded by the National Institute on Drug Abuse, the others by the National Institute on Alcoholism and Alcohol Abuse - by investigators associated with the Midwest Alcoholism Research Center at Washington University in St. Louis, and investigators at Queensland Institute of Medical Research, Brisbane, Australia (led by Professor Nicholas Martin), using informative families identified from these cohorts. The first of these (NIDA Nicotine Addiction Genetics [NAG] project, PI Pamela Madden) identified index cases from the 3 cohorts with a history of heavy smoking (smoked 20 or more cigarettes daily, or 40 or more cigarettes on 1 or more occasions) and with additional available full siblings who were smokers, and interviewed and obtained blood samples from twins, and cooperative full siblings and parents, in order to identify families that would be informative for linkage analysis of a quantitative heaviness of smoking trait. The second identified additional families with an index case who either reported a history of alcohol dependence (DSM-IV), or scored above the 85th percentile on a quantitative measure of heaviness of alcohol use (alcohol factor score), derived from measures of frequency of heavy drinking, frequency of drinking to intoxication, and typical weekly consumption in standard drinks (all referenced to the respondent's heaviest drinking period) and of lifetime maximum 1-day alcohol consumption and maximum tolerance to alcohol (drinks before getting drunk or before feeling effects of alcohol). Interview and DNA were obtained from index cases and siblings, and DNA only from available parents. The goal of this second study (NIAAA OZ-ALCOHOL EDAC study, PI Andrew Heath) was to identify sibships including pairs who were either extreme concordant for the quantitative consumption measure (both scoring above the 85th percentile) or extreme discordant (one scoring above the 85th percentile and one scoring below the 30th percentile) that would be informative for linkage analysis. The third identified additional sibships solely on the basis of large sibship size, regardless of alcohol or tobacco use phenotypes (NIAAA OZ-BIGSIB study, PIs the late Richard Todd, Andrew Heath). From these coordinated studies a case-control series of alcohol dependent individuals and unaffected controls were constructed for a family-based Genomewide Association Study (OZALC-GWAS) of heaviness of alcohol use and alcohol dependence, funded by the National Institute of Alcoholism and Alcohol Abuse. These data are made available here for all investigators studying outcomes related to alcohol or tobacco use (including major depressive disorder).</p>
| phs000181.v1.p1 | EGA
Project description:Context-induced relapse is a significant factor limiting recovery from alcohol use disorder (AUD). However, the molecular processes in the hippocampus, a critical region for contextual memory, impacted by chronic alcohol use remain poorly understood. We used a non-human primate model to test the hypothesis that chronic alcohol use impacts hippocampal molecular pathways that may serve as therapeutic targets for context-induced relapse and memory processing issues associated with chronic alcohol use. We conducted RNAseq profiling on hippocampal samples from adult male rhesus monkeys with chronic alcohol use (n=7) and controls (n=5) from the Monkey Alcohol Tissue Research Resource (MATRR). We identified 2,291 differentially expressed genes (DEGs) in subjects with chronic alcohol use, including genes implicated in genome-wide association studies (GWAS), such as GLP2R and GABBR2. Downregulated pathways included chemical synaptic transmission, trans-synaptic signaling, and neuron development, and upregulated pathways involved mitochondrial function. Targeted pathway analysis highlighted significant downregulation of synaptic signaling pathways (e.g., axonal fasciculation) and upregulation of mitochondrial processes (e.g., electron transport). Leading-edge analysis revealed several downregulated genes involved in synaptic signaling including GRIN2B, CACNA1C, and NLGN1 and upregulated genes such as NDUFS3 and MT-ND1 involved in mitochondrial processes. Drug repurposing analysis identified several targets including epidermal growth factor receptor (EGFR) inhibitors, and L-type calcium channel blockers as potential therapeutic targets. Our results provide critical insights into molecular pathways underlying hippocampal pathology in chronic alcohol use, emphasizing the roles of mitochondrial function, synaptic regulation and calcium channels in the hippocampus, and offering potential novel therapeutic targets.
2025-08-11 | GSE297855 | GEO
Project description:Tobacco use is an independent adverse prognostic feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Despite this, the biologic features associated with tobacco use have not been systematically investigated in this population. We sought to characterize the genomic and immunologic features of HPV(+) OPSCC associated with tobacco use and adverse oncologic outcomes. Whole exome sequencing of 47 primary HPV(+) OPSCC tumors was performed to investigate mutational differences associated with tobacco exposure. To characterize the tumor immune microenvironment (TIME), targeted mRNA hybridization was performed. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at the time of diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T>C substitutions and a lower proportion of mutational signatures typically observed in HPV(+) OPSCC tumors, but was not associated with increases in mutational burden or the rate of recurrent oncogenic mutations. Our work suggests that rather than increased mutational burden, tobacco’s primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment.
2022-04-02 | GSE199029 | GEO
Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol.
2013-11-06 | GSE49393 | GEO
Project description:Analysis of transcriptiomic alternations related with alcohol use disorders (AUDs). The hypothesis is that chronic alcohol consumption might alter genome-wide gene expression patterns. The results suggest that differential gene expression in the prefrontal cortex is implicated in neuroadaptations to alcohol.
2013-11-06 | GSE49376 | GEO
Project description:Excessive alcohol consumption is a leading cause of preventable death worldwide. Neurobiological mechanisms associated with alcohol use disorder (AUD) remain insufficiently understood. Here, we provide RNA-sequencing data generated in nucleus accumbent and dorsolateral prefrontal cortex, from 114 deceased individuals: 58 AUD cases, 56 non-AUD controls. DNA methylation data on many of these same individuals is available (see GEO accession number GSE252501).
2024-01-19 | GSE253155 | GEO
Project description:The present study utilized patient-derived “cell-line” model systems treated with anti-craving drugs that are used to treat alcohol use disorder (AUD) as “molecular probes” to help identify molecular mechanisms associated with craving and AUD treatment outcomes.
2024-04-03 | GSE213380 | GEO