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 奖项提案为 Helena Furberg 博士（一位受过经典培训的癌症流行病学家）提供了成为烟草预防和控制研究领域的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，以及基因组数据可用于流行病学研究的速度，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。在获奖的五年期间，她寻求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。获奖五年期间提出的活动通过专家导师参与所有四个实质性领域、相关课程和研讨会以及出席重要的国家会议，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）。将提供 2,000 名 25 至 47 岁瑞典人的详细烟草使用数据和 DNA 样本。 Furberg 博士建议对四个合理候选基因中的约 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培训将帮助她准确地对尼古丁依赖进行分类并考虑相关的混杂因素，遗传学培训将帮助她选择合理的候选基因，统计遗传学培训将教她如何将遗传信息整合到足以解决研究问题的大型关联研究中，ELSI 培训将帮助她深思熟虑地解释和传播结果。加深对尼古丁依赖机制的了解可能会导致更有效的治疗工作，从而有助于减少我们社会中与烟草相关的疾病的患病率。 Furberg 博士将从这个 K 奖中获得的技能将是终生的，并使她成为一名独立研究者，与不同领域的研究人员进行明智和创造性的合作，这种方法对于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，需要增加有关尼古丁成瘾遗传学的知识。该研究项目的结果将提供有关尼古丁成瘾个体差异的遗传原因的信息，这可能会导致更有效的吸烟治疗努力。

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