GENETICS OF NICOTINE AND OTHER ABUSED SUBSTANCES

描述(由申请者提供)：在这个由Kenneth Kendler博士赞助的陈向宁博士的科学家发展导师奖中，描述了一个为期5年的全面培训和研究计划，涉及尼古丁、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，遗传学影响物质使用行为。然而，这些遗传因素的性质在很大程度上仍不清楚。这些遗传因素的确定和特征将有助于药物滥用者和/或家属的预防、诊断和治疗。在该计划中，提出了促进职业发展和培养药物滥用和行为遗传学领域的独立研究的四个具体目标。目标是：1)。使用生物信息学工具和软件从连锁、微阵列、药理学和动物模型以及行为研究中选择、排序和优先考虑候选基因；2)使用从弗吉尼亚双胞胎注册中心挑选的病例对照样本来识别尼古丁依赖、酒精依赖和其他物质使用障碍的遗传风险因素；用为酒精依赖研究收集的新病例对照样本来验证目标2中确定的风险因素；以及4)。对目标2中使用的受试者的双胞胎的阳性标记进行基因分型，并使用结构方程建模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每种物质特有的还是在不同物质之间共享的。培训部分侧重于生物信息学技能、统计学原理和方法、滥用物质的神经化学和药理学以及药物滥用症状的分类和诊断。该提案将培训活动与研究计划相结合，以实现药物滥用遗传学领域的独立研究目标。

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.