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An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

ABSTRACT: An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

PROVIDER: PRJNA625893 | ENA |

REPOSITORIES: ENA

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An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

Project description:Cigarette smoking is one of the largest causes of preventable death worldwide. Smoking behaviors, including age at smoking initiation (ASI), smoking dependence (SD), and smoking cessation (SC), are all complex phenotypes determined by both genetic and environmental factors as well as their interactions. To identify susceptibility loci for each smoking phenotype, numerous studies have been conducted, with approaches including genome-wide linkage scans, candidate gene-based association analysis, and genome-wide association study (GWAS). Therefore, we conducted an exome-wide association study to identify new susceptibility loci for the risk of nicotine dependence in European-American populations.

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An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in African-American Populations

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Alcohol Dependence GWAS in European- and African Americans

Project description:This study includes SSADDA (Semi Structured Assessment for Drug Dependence and Alcoholism) assessed subjects (mostly unrelated, but including some affected sibling pairs) recruited in the course of several substance dependence genetics projects. The sample includes 1889 African-American (AA) subjects and 1020 European-American (EA) subjects. Among the AAs, 1397 meet DSM-IV criteria for alcohol dependence and 491 are controls. Among the EAs, 1010 meet the criteria for alcohol dependence and 9 are controls. (One in each population meets criteria for alcohol abuse and not dependence, and is therefore counted in neither category.) Although alcohol dependence is the major focus, the sample is informative also for cocaine, nicotine, and opioid dependence.

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Expression profiles and their potential roles of tRNA-derived small RNAs in hippocampus of nicotine dependence rat

Project description:The mechanism of nicotine dependence and nicotine related pain remains unclear. tRNAs, a major source of small noncoding RNAs (ncRNA), are the immediate areas of research focus, which have an important role in many pathophysiological processes. However, the role of tRNAs on nicotine dependence and related pain hasn’t been explored yet. In this study, our results indicated that the expression profiles of tRNAs have changed in nicotine treated rats as compared with normal rats, and among those, some differentially expressed tRNAs might be novel targets for nicotine dependence or nicotine related pain.

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deCODE Genetics study on genes contributing to nicotine dependence in humans

Project description:A genome-wide association study on smoking behavior and nicotine dependence in Icelandic smokers, assessed by the number of cigarettes smoked per day, smoking initiation and degree of dependence on nicotine. The number of cigarettes smoked per day was ascertained through questionnaires given to individuals participating in multiple disease projects at deCODE Genetics (n=16,483). Smoking initiation was analyzed by comparing those that have ever smoked (n=16,483) versus those that have never smoked (n=21,667). The nicotine dependence analysis included 3,435 nicotine dependent cases (score 4 or higher on Fagerstrom Test for Nicotine Dependence (FTND) or endorsement of at least three of the seven Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria) and 3,344 low-quantity smokers as controls.

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Tumor Immunobiological Differences in Prostate Cancer between African-American and European-American Men

Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Keywords: Microdissected tissue analysis

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