Novel Use of Gwas for Improved Understanding of Nicotine Dependence

描述(申请人提供)：通过这份K08申请，我请求帮助我过渡到一名统计遗传学的独立研究人员，应用于尼古丁依赖和共病精神障碍。我在统计学和临床精神病学方面都有基础，最近在精神病学和成瘾遗传学方面接受了博士后培训。这笔赠款将为我提供统计遗传学、数据收集、 赠款开发和项目管理。通过在数量遗传学(James Cheverud博士和Peter Kraft博士)、成瘾遗传学(Laura Bierut博士)、分子遗传学(Alison Goate博士)和精神病学遗传学(Michael Owen博士)导师的指导下进行授课和指导，我将发展成为一名成功的独立研究人员所需的专业知识。这项申请中提出的研究旨在为成瘾遗传学领域做出重大贡献，并通过利用我导师的技能来帮助我开发一个独立的研究领域，从而补充我的职业发展计划。这三个目标是(1)计算由全基因组关联研究中常见的SNPs解释的尼古丁依赖的表型变异的比例，以更好地理解数据集中可用的总信息量；(2)检查个体的同质性亚群并比较个体的亚群，以发现与尼古丁依赖更密切相关的新基因座，特别是在合并精神障碍的背景下；以及(3)开发一个数据库，以最大限度地发现导致尼古丁依赖的遗传变异。这些研究将帮助我制定一个强大的研究计划，利用我独特的量化专业知识与临床知识相结合，更好地理解吸烟和共病精神障碍的遗传学。

DESCRIPTION (provided by applicant): Through this K08 application, I request support to facilitate my transition to an independent researcher in statistical genetics as applied to nicotin dependence and comorbid psychiatric disorders. I have a foundation both in statistics and clinical psychiatry, and recent postdoctoral training in psychiatric and addiction genetics. This grant will provide me with the additional training I need in statistical genetics, data collection, grant development, and project management. Using a combination of didactic coursework and supervision with mentors in quantitative genetics (Drs. James Cheverud, and Peter Kraft), addiction genetics (Dr. Laura Bierut), molecular genetics (Dr. Alison Goate), and psychiatric genetics (Dr. Michael Owen), I will develop the expertise needed to become a successful, independent investigator. The research proposed in this application was designed to significantly contribute to the field of addiction genetics, and to complement my career development plan by leveraging the skills of my mentors to help guide me to develop an independent field of study. The three aims are (1) to calculate the proportion of phenotypic variance for nicotine dependence that is explained by the common SNPs in genome-wide association studies (GWAS) to better understand the total amount of information available in the datasets, (2) to examine homogenous subgroups of individuals and compare contrasting subgroups of individuals to find novel loci that are more strongly associated with nicotine dependence, particularly in the context of comorbid psychiatric disorders, and (3) to develop a database to maximize power for discovery of genetic variants that contribute to nicotine dependence. These studies will help me to develop a strong research program that uses my unique combination of quantitative expertise with clinical knowledge to better understand the genetics of smoking and comorbid psychiatric disorders.