Genetic and Environmental Risks for Smoking Characteristics and Cessation

吸烟特征和戒烟的遗传和环境风险

• 批准号: 8325014
• 负责人: Li-Shiun Chen
• 金额: $ 16.78万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325014
• 关键词: Abstinence; Accounting; Affect; African American; Award; Behavioral; Biological; Cessation Research; Characteristics; Cigarette; Clinical; Comorbidity; Country; DSM-IV; Data; Data Analyses; Data Collection; Data Set; Dependence; Development; Diagnosis; Diagnostic and Statistical Manual; Disease; Environment; Environmental Risk Factor; Epidemiology; Equipment and supply inventories; Etiology; European; Family; Follow-Up Studies; Foundations; Future; General Population; Genetic; Genetic Predisposition to Disease; Genetic Risk; Goals; Hand; Health Care Costs; Heritability; Knowledge; Link; Literature; Measures; Mental disorders; Methods; Morbidity - disease rate; Nicotine Dependence; Outcome; Outcomes Research; Phenotype; Population; Prevention; Probability; Prospective Studies; Psychiatrist; Public Health; Relapse; Research; Research Methodology; Research Personnel; Research Training; Rice; Sampling; Science; Smoker; Smoking; Smoking Behavior; Syndrome; Testing; Time; Tobacco; Training; Transdisciplinary Tobacco Research Center; Translating; Treatment Factor; Universities; Variant; Washington; Wisconsin; Withholding Treatment; Work; career; cigarette smoking; economic cost; experience; follow-up; genetic association; genetic variant; genome wide association study; innovation; insight; mortality; novel; peer; programs; prospective; psychogenetics; smoking cessation; success; treatment strategy

DESCRIPTION (provided by applicant): I request support through the K08 award to complete my transition from a clinical board-certified psychiatrist with prior research training in epidemiology to an independent translational researcher in genetic and environmental factors for smoking cessation. To achieve this goal, I need further training and experience in advanced genetics, cessation science, and longitudinal research methods, to enable me to conduct future prospective studies on genetics of smoking cessation. I will be guided by experts in the fields of advanced genetics (Drs. Laura Bierut, Alison Goate, John Rice, and Robi Mitra), cessation science (Drs. Timothy Baker and Gary Swan), and longitudinal research (Drs. Naomi Breslau, Eric Johnson, Laura Bierut, and Timothy Baker). The training goals will be advanced through the following proposed research on nicotine dependence which is a serious public health problem. Some genetic variants associated with nicotine dependence and smoking cessation have been identified with modern genetic methods, but account for only a small amount of genetic variance. Our preliminary results suggest comprehensive nicotine dependence phenotypes and prospective cessation measures have greater sensitivity to detect genetic associations. This study aims to fill gaps in the research literature by conducting (1) Genome Wide Association Study (GWAS) analyses of nicotine dependence using comprehensive novel phenotypes in two existing, complementary datasets (population vs. treatment sample), (2) GWAS analyses of prospective smoking cessation phenotype, and (3) a pilot longitudinal follow up study of nicotine dependence subjects to replicate the genetic findings of smoking cessation from study aim 2, and to examine identified genetic risks jointly with environmental, comorbid, and treatment factors. We hope to uncover novel genetic variants associated with refined phenotypic characteristics of nicotine dependence and smoking cessation. Genetic risks associated with smoking cessation may be different from those for nicotine dependence, and this distinction will be useful in translating genetic risk to outcome research. Knowledge of how genetic risks influence clinical outcomes and whether they are modified by treatment and comorbid disorder factors will not only clarify the etiology of nicotine dependence to create opportunity for prevention, but also provide needed evidence for individualized cessation treatments to increase the probability of successful quitting. This will be the foundation for future R01 applications for large scale, prospective studies of smoking cessation trials. In summary, by the end of this award, I will become an expert in psychiatric genetics with a focus on smoking cessation. Through my training in advanced genetic methods, cessation science, and longitudinal analyses, along with hands on experience in longitudinal data collection and analyses, I will establish a unique smoking cessation research program at Washington University and launch an independent career conducting large scale smoking cessation trials that will make important contributions to the treatment of nicotine dependence and related disorders.

描述（由申请人提供）：我要求通过K08 Award提供支持，以完成我从临床董事会认证的精神科医生的过渡，并在流行病学的先前研究培训中，再到遗传和环境戒烟环境因素的独立转化研究人员。为了实现这一目标，我需要在先进的遗传学，戒烟科学和纵向研究方法方面进行进一步的培训和经验，以使我能够对戒烟的遗传学进行未来的前瞻性研究。我将受到高级遗传学领域的专家（Laura Bierut博士，Alison Goate，John Rice和Robi Mitra）的指导，戒烟科学（Timothy Baker和Gary Swan博士）以及纵向研究（Dr.Noomi Breslau，Eric Johnson，Laura Bierut和Timothyut and Timothy和Timothy Baker）。培训目标将通过以下提议的尼古丁依赖研究提出，这是一个严重的公共卫生问题。与尼古丁依赖性和戒烟相关的一些遗传变异已通过现代遗传学方法鉴定出来，但仅解释了少量的遗传方差。我们的初步结果表明，综合的尼古丁依赖表型和前瞻性停止措施对检测遗传关联具有更大的敏感性。这项研究旨在通过进行（1）基因组广泛关联研究（GWAS）分析尼古丁的依赖性（GWAS）在两个现有的新型表型中对尼古丁依赖性的分析（GWAS）分析，该表型在两个现有的补充数据集（人口与治疗样本），（2）GWAS分析的gwas分析，对前瞻性吸烟的依赖性依赖性依赖性的依赖性依赖性的依赖性依赖性，（3），（3）对（3）的依赖性依赖性的依赖性，（3）。从研究目标2戒烟，并与环境，合并和治疗因素共同检查确定的遗传风险。我们希望发现与尼古丁依赖性和戒烟的精制表型特征相关的新型遗传变异。与戒烟相关的遗传风险可能与尼古丁依赖性不同，这种区别将有助于将遗传风险转化为结果研究。了解遗传风险如何影响临床结果以及它们是否通过治疗和合并症的因素进行修改，不仅会阐明尼古丁依赖性的病因，从而为预防创造机会，而且还为个性化戒烟治疗提供了所需的证据，以增加成功退出的可能性。这将是对戒烟试验的大规模，前瞻性研究的未来R01申请的基础。总而言之，到该奖项结束时，我将成为精神病遗传学专家，专注于戒烟。通过我对高级遗传方法，戒烟科学和纵向分析的培训，以及在纵向数据收集和分析方面的经验，我将在华盛顿大学建立一个独特的吸烟戒烟研究计划，并启动独立的职业，从事大规模的吸烟戒烟试验，该试验将对治疗尼古丁依赖和相关性分歧做出重要贡献。