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了证据，表明基因在滥用酒精和烟草中起着重要作用。此外，流行病学和生物遗传学研究表明，酒精和烟草使用之间的合并症很高，这可能是由于遗传因素重叠所致。来自药理学研究的融合证据以及与酒精和烟草相关表型的小鼠模型的研究也支持了以下假设：两种物质都激活了相同的神经系统途径。最近的证据表明，神经元烟碱受体（NACHR）是这些药物的关键靶标。已知几种烟碱受体参与介导对酒精和尼古丁的响应释放。这些受体（alpha4-6和beta2-3亚基）在调节多巴胺能奖励途径中可能起重要作用，这与有助于与药物使用相关的令人愉悦的感觉有很大的影响。该项目旨在检查Alpha4-6，Beta2-3 NACHR亚基的基因，以便它们在促进酒精和烟草问题的发展中的作用。候选人将在兄弟姐妹对样本中检查这些基因，DMA和表型数据已被作为国家青少年健康纵向研究（ADD HEALTY）的一部分。候选人将利用计算生物信息学方法来识别这些基因中潜在的功能性单核苷酸多态性（SNP），以便在受试者中最佳选择SNP并确定这些基因型。几种统计方法将用于测试与单个SNP或单倍型以及酒精或烟草问题使用的关联和/或链接的结合。执行生物信息学和统计遗传学的技能将通过课程，研讨会，讲习班，会议和与导师的磋商来开发。 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使用障碍专家进行定期互动。该项目将使候选人能够实现她学习计算生物信息学方法的短期目标，以及先进的统计遗传学方法来分析数据，同时积累证据表明这些基因可能有助于酒精和烟草问题使用。这还将促进她的长期职业目标，即建立在酒精和烟草使用行为遗传学方面的独立研究职业，并为将来的研究提供基础。