The Genetic Epidemiology of Nicotine Dependence

尼古丁依赖的遗传流行病学

• 批准号: 7937973
• 负责人: Anna Helena Furberg-Barnes
• 金额: $ 10.81万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-07 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937973
• 关键词: Address; Adoption; Affect; Age; Age-Years; Alcohol consumption; Area; Award; Biology; Body Size; Brain; Candidate Disease Gene; Characteristics; Complement; DNA; DRD2 gene; DSM-IV; Data; Dopamine; Dopamine Receptor; Educational Background; Educational process of instructing; Educational workshop; Ensure; Environmental Risk Factor; Enzymes; Epidemiologic Studies; Epidemiologist; Equilibrium; Etiology; Family; Frequencies; Funding; Gender; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Research; Genetic Variation; Genomics; Genotype; Haplotypes; Hepatic; Human Genetics; Individual; Individual Differences; Informed Consent; Intervention; K-Series Research Career Programs; Knowledge; Lead; Life; Malignant Neoplasms; Marital Status; Mentors; Meta-Analysis; Metabolism; Molecular Genetics; Morbidity - disease rate; Nicotine; Nicotine Dependence; Nicotinic Receptors; Pathway interactions; Personality Traits; Phenotype; Physical activity; Play; Population; Positioning Attribute; Prevalence; Prevention; Principal Investigator; Research; Research Activity; Research Personnel; Research Project Grants; Review Literature; Rewards; Risk; Role; Sampling; Smoker; Smoking Behavior; Societies; Specimen; Staging; Sweden; Synapses; Technology; Time; Tobacco; Tobacco use; Training; Training Activity; Twin Multiple Birth; Ventral Tegmental Area; Work; addiction; base; cancer epidemiology; case control; cigarette smoking; cytochrome P-450 CYP2A6 (human); design; dopamine transporter; effective therapy; epidemiology study; ethical legal social implication; experience; genetic epidemiology; human study; meetings; mortality; mouse model; programs; public health relevance; receptor function; research study; reuptake; skills; smoking cessation; tobacco prevention

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.

描述（由申请人提供）：该K07奖励提案提供了经典培训的癌症流行病学家Helena Furberg博士所需的培训和研究活动，以成为预防烟草预防和控制研究中独立的遗传流行病学家。鉴于尼古丁依赖性的复杂性，以及用于流行病学研究的基因组数据的速率，弗伯格博士必须发展深入的知识并扩大技能集，以适当地设计，进行，分析，解释和传播此信息。在奖项的五年中，她在癌症流行病学背景的特定领域寻求正式培训：1）尼古丁依赖表型，2）分子遗传学，3）统计遗传学，4）人类遗传研究的伦理，法律和社会意义。该奖项五年期间提出的活动通过在所有四个实体领域的专家导师参与，相关的课程和讲习班以及参加重要的全国会议上的智能挑战。她通过培训活动获得的知识将直接应用于尼古丁依赖性的遗传流行病学研究，该研究嵌套在一项大型NCI资助的戒烟研究中（PI：Patrick Sullivan博士，该奖项的主要导师Patrick Sullivan博士）。详细的烟草使用数据和DNA标本将在25至47岁之间的2,000名瑞典人上提供。 Furberg博士提出了四个有理候选基因的基因型〜70个遗传标记，并评估与尼古丁依赖性有关的关联。她在成瘾生物学和烟草使用评估中接受的培训将有助于她准确地对尼古丁的依赖性进行分类并考虑相关的混杂因素，遗传学培训将为她选择合理的候选基因的选择，统计遗传学的培训将教导她如何将遗传信息整合到大型关联研究中，以解决研究问题，以解决研究问题和Elsi的培训，并有助于分散的结果，并经过思考和思考。对尼古丁依赖涉及的机制的更多了解可能会导致更有效的治疗工作，从而有助于降低我们社会中与烟草相关疾病的患病率。 Furberg博士将从该K奖中获得的技能是终身的，并将使她成为一名独立的调查员，他与不同领域的研究人员聪明，创造性地合作，这种方法对于对所有癌症的进步至关重要。公共卫生相关性：为了减少癌症发病率和死亡率，需要越来越多的尼古丁成瘾遗传学知识。该研究项目的发现将为尼古丁成瘾中个体差异的遗传原因提供信息，这可能会导致吸烟的更有效治疗工作。

项目成果

Is low-nicotine Marlboro snus really snus?

• DOI: 10.1186/1477-7517-5-9
• 发表时间: 2008-01-01
• 期刊: HARM REDUCTION JOURNAL
• 影响因子: 4.4
• 作者: Foulds, Jonathan;Furberg, Helena
• 通讯作者: Furberg, Helena

Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases.

• DOI: 10.1093/aje/kwp119
• 发表时间: 2009-08-01
• 期刊: American journal of epidemiology
• 影响因子: 5
• 作者: Khoury MJ;Bertram L;Boffetta P;Butterworth AS;Chanock SJ;Dolan SM;Fortier I;Garcia-Closas M;Gwinn M;Higgins JP;Janssens AC;Ostell J;Owen RP;Pagon RA;Rebbeck TR;Rothman N;Bernstein JL;Burton PR;Campbell H;Chockalingam A;Furberg H;Little J;O'Brien TR;Seminara D;Vineis P;Winn DM;Yu W;Ioannidis JP
• 通讯作者: Ioannidis JP