Genetic Variants and Tobacco Use in Chinese Adolescents

中国青少年的基因变异与烟草使用

• 批准号: 7286759
• 负责人: David V Conti
• 金额: $ 41.12万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7286759
• 关键词: Chinese; adolescence (12-20); behavioral /social science research tag; behavioral genetics; clinical research; dopamine; genetic mapping; genetic polymorphism; genetic susceptibility; genotype; high throughput technology; human subject; serotonin; single nucleotide polymorphism; substance abuse epidemiology; substance abuse related behavior; tobacco abuse; tobacco abuse prevention

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.

项目3：中国青少年的遗传变异和烟草使用 中国青少年项目中遗传变异和烟草使用的目的是更好地了解吸烟行为的遗传贡献。 USC TTURC的前四年的结果表明，个人性格和文化背景对预防计划具有潜在的重要主持人影响。在这个项目中，我们假设负责敌对和抑郁等造成牙齿属性的遗传因素既影响个人的吸烟行为，又可以调节烟草控制干预和预防试验的有效性。为此，我们将对遗传学的遗传流行病学研究 血清素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外，我们还将在来自中国武汉现有队列的2,661名学生中的17个候选基因中的250个SNP基因型。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分析和DNA测序，将用于全面介绍候选基因中的遗传变异。我们将研究这些多态性与施加属性的关系，例如敌对和抑郁，吸烟和酒精使用结果。此外，我们将研究这些多态性的重要相互作用效应，并结合倾向属性和基于学校的干预计划的影响。我们将实施层次建模，以包括有关5-羟色胺和多巴胺系统的生物学机制的知识，以及贝叶斯模型的平均模型，以全面评估最能代表多方面社会环境中吸烟行为基本复杂性的风险因素集。拟议研究的结果 应该增强我们对吸烟的遗传易感性的了解，并允许我们创建更有效的预防计划，这些计划是专门针对这项工作中确定的各个子组量身定制的。