GENETICS OF NICOTINE AND OTHER ABUSED SUBSTANCES

描述（由申请人提供）：在这个由Kenneth Kendler博士赞助的导师科学家发展奖中，陈香宁博士描述了一个为期5年的全面培训和研究计划，用于尼古丁，酒精和其他滥用物质的遗传学。吸烟、酗酒和滥用药物是严重的公共卫生问题。流行病学研究表明，基因会影响物质使用行为。然而，这些遗传因素的性质在很大程度上仍然未知。查明和确定这些遗传因素将有助于预防、诊断和治疗药物滥用者和/或依赖者。在该计划中，提出了四个具体目标，以促进专业成长，培养药物滥用和行为遗传学领域的独立研究。目标是：1)。使用生物信息学工具和软件从连锁、微阵列、药理学、动物模型和行为研究中选择、排序和优先考虑候选基因；2）.使用从弗吉尼亚双胞胎登记处选择的病例对照样本来确定尼古丁依赖、酒精依赖和其他物质使用障碍的遗传风险因素；3)。通过为酒精依赖研究收集的新病例对照样本验证目的2中确定的危险因素；和4)。对目标2中使用的受试者的阳性标记进行基因分型，并使用结构方程模型和其他统计技术来测试目标2和目标3中确定的遗传风险因素是否特定于每种物质或在不同物质之间共享。培训内容侧重于生物信息学技能、统计原理和方法、滥用药物的神经化学和药理学以及药物滥用症状的分类和诊断。该建议将培训活动与研究计划结合起来，以实现在药物滥用遗传学领域进行独立研究的目标。

DESCRIPTION (provided by applicant): In this mentored scientist development award for Dr. Xiangning Chen, sponsored by Dr. Kenneth Kendler, describes a 5-year, comprehensive training and research program for the genetics of nicotine, alcohol and other abused substances. Tobacco smoking, alcoholism and drug abuses are serious public health issues. Epidemiology studies have shown that genetics influences the behaviors of substance uses. However, the nature of these genetic factors remains largely unknown. The identification and characterization of these genetic factors would facilitate the prevention, diagnosis and treatment of substance abusers and/or dependents. In the program, four specific aims are proposed to facilitate professional growth and to cultivate independent research in the fields of substance abuse and behavioral genetics. The aims are: 1). To use bioinformatic tools and software to select, rank and prioritize candidate genes from linkage, microarray, pharmacology and animal model and behavioral studies; 2).To use a case-control sample selected from the Virginia Twin Registry to identify genetic risk factors for nicotine dependence, alcohol dependence and other substance use disorders; 3). To verify risk factors identified from aim 2 with a new case-control sample collected for alcohol dependence studies; and 4). To genotype those positive markers for the cotwins of subjects used in aim 2 and to use structural equation modeling and other statistical techniques to test if genetic risk factors identified in aims 2 and 3 are specific to each substance or shared between different substances. The training components focus on bioinformatics skills, statistical principles and methods, neural chemistry and pharmacology of abused substances and classification and diagnosis of substance abuse symptoms. The proposal integrates the training activities with the research plan to achieve the goal of independent research in the fields of drug abuse genetics.