Genetic Variants and Tobacco Use in Chinese Adolescents

项目3：中国青少年的基因变异和烟草使用 基因变异和中国青少年烟草使用项目的目的是为了更好地了解基因对吸烟行为的影响。南加州大学TTURC头四年的结果表明，个人性格和文化背景对预防计划具有潜在的重要调节作用。在这个项目中，我们假设导致倾向属性的遗传因素，如敌意和抑郁，既影响个人的吸烟行为，又影响控烟干预和预防试验的有效性。为此，我们将进行一项基因流行病学研究 5-羟色胺和多巴胺系统中关键候选基因的多态及其对烟草使用的影响。除了已知的功能变异外，我们还将对来自武汉的现有队列中的2,661名学生中国的17个候选基因中的250多个SNPs进行基因分型。基因组技术的组合，包括光纤阵列上的高通量SNP基因分型、基因扫描、Taqman分析和DNA测序，将被用来全面描述候选基因的遗传变异。我们将调查这些多态与性格特征的关系，例如敌意和抑郁，以及吸烟和饮酒的结果。此外，我们还将结合性格特征和学校干预计划的影响来检验这些多态的重要交互作用。我们将实施分层建模，以包括关于5-羟色胺和多巴胺系统的生物学机制的知识，并将贝叶斯模型平均，以综合评估在多方面社会背景下最能代表吸烟行为潜在复杂性的风险因素集。拟议研究的结果 应该加强我们对吸烟遗传易感性的了解，并使我们能够制定更有效的预防方案，专门针对这项工作中确定的不同亚群制定。

Project 3: Genetic Variants and Tobacco Use in Chinese Adolescents The aim of the Genetic Variants and Tobacco Use in Chinese Adolescents project is to better understand the genetic contribution to smoking behavior. Results from the first four years of the USC TTURC indicate that individual disposition and cultural context have a potentially important moderator effect on prevention programs. In this project, we hypothesize that genetic factors responsible for dispositional attributes, such as hostility and depression, act to both influence an individual's smoking behavior and to moderate the effectiveness of tobacco control intervention and prevention trials. To this end, we will conduct a genetic epidemiologic study of genetic polymorphisms in key candidate genes within the serotonin and dopamine systems and their impact on tobacco use. In addition to known functional variants, we will genotype over 250 SNPs in 17 candidate genes in 2,661 students from an existing cohort from Wuhan, China. A combination of genomic technologies, including highthroughput SNP genotyping on fiber optic array, GeneScan, Taqman assay and DNA sequencing, will be used to comprehensively profile genetic variations in the candidate genes. We will investigate the relation of these polymorphisms to dispositional attributes, such as hostility and depression, and smoking and alcohol use outcomes. Additionally, we will examine important interaction effects of these polymorphisms combined with the effects from dispositional attributes and from a school-based intervention program. We will implement hierarchical modeling to include knowledge regarding the biological mechanism for the serotonin and dopamine systems and Bayes model averaging to comprehensively evaluate the set of risk factors that best represents the underlying complexity of smoking behavior within a multifaceted social context. The results of the proposed study should enhance our knowledge of genetic predisposition to smoking and allow us to create more effective prevention programs that are specifically tailored to the various subgroups identified in this work.