The Genetic Epidemiology of Nicotine Dependence

描述（由申请人提供）：本K07奖提案为受过经典训练的癌症流行病学家Helena Furberg博士提供了成为烟草预防和控制研究领域独立遗传流行病学家所需的培训和研究活动。考虑到尼古丁依赖的复杂性，以及基因组数据在流行病学研究中可用的速度，Furberg博士必须发展深厚的知识和扩展的技能，以便适当地设计、实施、分析、解释和传播这些信息。在该奖项的五年中，她寻求在特定领域的正式培训，以补充她在癌症流行病学方面的背景：1)尼古丁依赖表型，2)分子遗传学，3)统计遗传学，以及4)人类基因研究的伦理，法律和社会影响。在该奖项的五年中提出的活动通过专家导师参与所有四个实质性领域，相关课程和讲习班以及参加重要的国家会议，对她提出了明智的挑战。她通过培训活动获得的知识将直接应用于尼古丁依赖的遗传流行病学研究，该研究嵌套在nci资助的大型戒烟研究中（PI: Patrick Sullivan博士，该奖项的主要导师）。2000名年龄在25岁至47岁之间的瑞典人将获得详细的烟草使用数据和DNA样本。Furberg博士建议对四个合理的候选基因中的70个遗传标记进行基因分型，并评估与尼古丁依赖相关的关联。她接受的成瘾生物学和烟草使用评估方面的培训将帮助她准确地分类尼古丁依赖并考虑相关的混杂因素，遗传学方面的培训将告诉她选择合理的候选基因，统计遗传学方面的培训将教会她如何将遗传信息整合到一个大型的关联研究中，以充分解决研究问题，ELSI培训将帮助她深思熟虑地解释和传播结果。对尼古丁依赖机制的进一步了解可能会导致更有效的治疗措施，从而有助于减少我们社会中与烟草有关的疾病的流行。Furberg博士将从这个K奖中获得终身的技能，并将使她成为一名独立的研究者，与不同领域的研究人员进行智能和创造性的合作，这种方法对对抗所有癌症的进展至关重要。公共卫生相关性：为了降低癌症发病率和死亡率，需要增加对尼古丁成瘾基因的了解。这项研究项目的发现将有助于了解尼古丁成瘾个体差异的遗传原因，这可能会导致更有效的治疗吸烟的努力。

DESCRIPTION (provided by applicant): This K07 award proposal provides the training and research activities required for Dr. Helena Furberg, a classically trained cancer epidemiologist, to become an independent genetic epidemiologist in tobacco prevention and control research. Given the complexity of nicotine dependence, and the rate at which genomic data are becoming available for use in epidemiological studies, Dr. Furberg must develop a deep knowledge and expanded skill set in order to design, conduct, analyze, interpret, and disseminate this information appropriately. During five years of the award, she seeks formal training in specific areas that complement her background in cancer epidemiology: 1) the nicotine dependence phenotype, 2) molecular genetics, 3) statistical genetics, and 4) the ethical, legal, and social implications of human genetic research. The activities proposed during the five years of the award challenge her intelligently through expert mentor involvement in all four substantive areas, relevant coursework and workshops, and attendance at key national meetings. The knowledge she acquires through the training activities will be applied directly to a genetic epidemiology study of nicotine dependence, nested within a large NCI-funded study of smoking cessation (PI: Dr. Patrick Sullivan, primary mentor on this award). Detailed tobacco use data and DNA specimens will be available on 2,000 Swedish individuals between 25 and 47 years of age. Dr. Furberg proposes to genotype ~70 genetic markers in four rational candidate genes and evaluate associations in relation to nicotine dependence. The training she receives in addiction biology and tobacco use assessment will help her accurately classify nicotine dependence and consider relevant confounders, training in genetics will inform her selection of plausible candidate genes, training in statistical genetics will teach her how to integrate genetic information into a large association study adequately powered to address the research questions, and ELSI training will assist her in thoughtfully interpreting and disseminating the results. An increased understanding of the mechanisms involved in nicotine dependence could lead to more effective treatment efforts, and consequently contribute to a decrease in the prevalence of tobacco-related illnesses in our society. The skills Dr. Furberg will acquire from this K award are life-long and will position her to become an independent investigator who collaborates intelligently and creatively with researchers in different fields, an approach that is critical for progress against all cancers. Public Health Relevance: In order to achieve reductions in cancer morbidity and mortality, increased knowledge about the genetics of nicotine addiction are needed. Findings from this research project will contribute information on genetic reasons for individual differences in nicotine addiction, which could lead to more effective treatment efforts for cigarette smoking.