Genetic Variants and Tobacco Use in Chinese Adolescents

项目3：中国青少年的遗传变异和烟草使用 中国青少年的遗传变异和烟草使用项目的目的是更好地了解遗传因素对吸烟行为的影响。南加州大学TTURC的前四年的结果表明，个人的性格和文化背景有一个潜在的重要的调节作用的预防计划。在这个项目中，我们假设，遗传因素负责的性格属性，如敌意和抑郁症，既影响个人的吸烟行为和适度的烟草控制干预和预防试验的有效性。为此，我们将进行一项遗传流行病学研究， 5-羟色胺和多巴胺系统中关键候选基因的多态性及其对烟草使用的影响。除了已知的功能变体，我们还将对来自中国武汉现有队列的2，661名学生的17个候选基因中的250多个SNP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、GeneScan、Taqman测定和DNA测序，将用于全面分析候选基因中的遗传变异。我们将调查这些多态性与性格属性的关系，如敌意和抑郁，吸烟和饮酒的结果。此外，我们将研究这些多态性的重要的相互作用的影响，结合从性格属性和以学校为基础的干预计划的影响。我们将实施分层建模，包括有关血清素和多巴胺系统的生物机制的知识，以及贝叶斯模型平均，以全面评估最能代表多方面社会背景下吸烟行为潜在复杂性的一组风险因素。拟议研究的结果 应该提高我们对吸烟遗传易感性的认识，并使我们能够制定更有效的预防计划，专门针对这项工作中确定的各种亚组。

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.