Molecular Genetics and Behavior: Alcohol and Tobacco Use

描述(由申请人提供)：双胞胎、收养和家庭研究已经提供了证据，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遗传学研究表明，饮酒和吸烟之间有很高的共患率，这可能是由于重叠的遗传因素造成的。来自药理学研究和对与酒精和烟草相关的表型的小鼠模型的研究的融合证据也支持这样的假设，即这两种物质激活了相同的神经通路。最近的证据表明，神经元尼古丁受体(NAChRs)是这些药物的关键靶点。已知有几种尼古丁受体参与调节多巴胺对酒精和尼古丁的反应。这些受体(α4-6和β2-3亚单位)可能在调节多巴胺能奖赏通路中发挥重要作用，多巴胺能奖赏通路强烈地参与了与物质使用相关的愉悦感觉的贡献。该项目旨在研究α4-6、β2-3 nAChR亚单位的基因，以寻找它们在促进酒精和烟草问题使用方面的可能作用。候选人将在兄弟姐妹中检查这些基因，这些兄弟姐妹的DMA和表型数据已经作为国家青少年健康纵向研究(ADD Health)的一部分收集了。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(SNPs)，以便最佳地选择SNPs并确定受试者中这些SNPs的基因类型。将使用几种统计方法来测试与单个SNP或单倍型以及酒精或烟草问题的使用之间的关联和/或联系。进行生物信息学和统计遗传学的技能将通过课程作业、研讨会、研讨会、会议和与导师的咨询来发展。 培训将在行为遗传学研究所进行，这是一个独特的环境，候选人将在那里与行为遗传学和物质使用障碍方面的专家定期互动。该项目将使候选人能够实现她的短期目标，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，同时积累这些基因可能导致酒精和烟草问题使用的证据。这也将促进她在酒精和烟草使用的行为遗传学方面建立独立研究生涯的长期职业目标，并为未来的研究提供基础。

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.