Molecular Genetics and Behavior: Alcohol and Tobacco Use

分子遗传学和行为：酒精和烟草的使用

• 批准号: 7490510
• 负责人: MARISSA A EHRINGER
• 金额: $ 13.59万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490510
• 关键词: Adolescent; Adoption; Affect; Alcohol abuse; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; Animals; Behavioral Genetics; Bioinformatics; Comorbidity; Complex; Consultations; Data; Data Analyses; Development; Disease; Dopamine; Drosophila acetylcholine receptor alpha-subunit; Drug Delivery Systems; Educational workshop; Environment; Evaluation; Family Study; Feeling; Foundations; Future; Gene Expression Regulation; Genes; Genetic; Genomics; Genotype; Goals; Haplotypes; Health; Individual; Institutes; Learning; Linkage Disequilibrium; Longitudinal Studies; Mediating; Mentors; Methods; Molecular; Molecular Genetics; Mutation; Neurologic; Neurons; Nicotine; Nicotinic Receptors; Pathway interactions; Phenotype; Play; Quantitative Genetics; RNA Splicing; Receptor Gene; Research; Resources; Rewards; Role; Rosa; Sampling; Siblings; Single Nucleotide Polymorphism; Smoking; Statistical Methods; Substance Use Disorder; System; Testing; Tobacco; Tobacco use; Training; Translational Research; Twin Multiple Birth; Variant; Wit; alcohol behavior; alcohol response; base; career; mouse model; novel strategies; receptor; research study; response; skills; symposium; tobacco abuse

DESCRIPTION (provided by applicant): Twin, adoption, and family studies have provided evidence that genes play an important role in alcohol and tobacco abuse. Moreover, epidemiological and biometrical genetics studies have shown that there is high comorbidity between alcohol and tobacco use, which may be due to overlapping genetic factors. Converging evidence from pharmacological research and the study of mouse models of alcohol- and tobacco-related phenotypes also supports the hypothesis that the same neurological pathways are activated by both substances. Recent evidence has implicated the neuronal nicotinic receptors (nAChRs) as critical targets of these drugs. Several nicotinic receptors are known to be involved in mediating the release of dopamine in response to alcohol and nicotine. These receptors (the alpha4-6 and beta2-3 subunits) may play an important role in regulating the dopaminergic reward pathway, which has been strongly implicated in contributing to the pleasurable feelings associated with substance use. This project seeks to examine the genes for the alpha4-6, beta2-3 nAChR subunits for their possible role in contributing to the development of alcohol and tobacco problem use. The candidate will examine these genes in a sample of sibling pairs for which DMA and phenotypic data have already been collected as a part of the National Longitudinal Study of Adolescent Health (Add Health). The candidate will utilize computational bioinformatics methods to identify potential functional single nucleotide polymorphisms (SNPs) within these genes in order to optimally select the SNPs and determine the genotypes of these in the subjects. Several statistical methods will be used to test for association and/or linkage with individual SNPs or haplotypes and alcohol or tobacco problem use. The skills to perform bioinformatics and statistical genetics will be developed through coursework, symposia, workshops, conferences, and consultations with mentors. Training will take place at the Institute for Behavioral Genetics, a unique environment where the candidate will have regular interactions with experts in behavior genetics and substance use disorders. This project will allow the candidate to achieve her short-term goals of learning computational bioinformatics methods, as well as advanced statistical genetics methods to analyze the data, while accumulating evidence that these genes may contribute to alcohol and tobacco problem use. It will also promote her long-term career goals of establishing an independent research career in behavior genetics of alcohol and tobacco use and provide a foundation for future studies.

描述（由申请人提供）：双胞胎、收养和家庭研究提供的证据表明，基因在酗酒和吸烟中发挥着重要作用。此外，流行病学和生物统计学研究表明，饮酒和吸烟之间存在高度共病，这可能是由于重叠的遗传因素造成的。来自药理学研究以及酒精和烟草相关表型的小鼠模型研究的综合证据也支持了两种物质激活相同神经通路的假设。最近的证据表明神经元烟碱受体（nAChR）是这些药物的关键靶点。已知几种烟碱受体参与介导响应酒精和尼古丁的多巴胺释放。这些受体（α4-6 和 β2-3 亚基）可能在调节多巴胺能奖赏通路中发挥重要作用，该通路与物质使用相关的愉悦感密切相关。该项目旨在检查 α4-6、β2-3 nAChR 亚基的基因，了解它们在促进酒精和烟草使用问题的发展中可能发挥的作用。候选人将检查兄弟姐妹对样本中的这些基因，这些样本的 DMA 和表型数据已作为国家青少年健康纵向研究 (Add Health) 的一部分收集。候选人将利用计算生物信息学方法来识别这些基因内潜在的功能性单核苷酸多态性 (SNP)，以便最佳地选择 SNP 并确定受试者中这些 SNP 的基因型。将使用几种统计方法来测试与个体 SNP 或单倍型以及酒精或烟草问题使用的关联和/或联系。生物信息学和统计遗传学的技能将通过课程、研讨会、研讨会、会议和与导师的咨询来培养。 培训将在行为遗传学研究所进行，这是一个独特的环境，候选人将与行为遗传学和药物滥用障碍方面的专家定期互动。该项目将使候选人能够实现学习计算生物信息学方法以及先进的统计遗传学方法来分析数据的短期目标，同时积累这些基因可能导致酗酒和吸烟问题的证据。它还将促进她在酒精和烟草使用行为遗传学方面建立独立研究事业的长期职业目标，并为未来的研究奠定基础。