Novel Use of Gwas for Improved Understanding of Nicotine Dependence

描述（由申请人提供）：通过此K08申请，我请求支持，以促进我过渡到统计遗传学的独立研究人员，适用于尼古丁依赖和共病精神疾病。我有统计学和临床精神病学的基础，最近还接受了精神病学和成瘾遗传学的博士后培训。这笔赠款将为我提供额外的培训，我需要在统计遗传学，数据收集， 赠款开发和项目管理。使用教学课程和监督与导师在数量遗传学（博士詹姆斯Cheverud，和彼得卡夫）相结合，成瘾遗传学（博士劳拉Bierut），分子遗传学（博士艾莉森Goate），和精神遗传学（博士迈克尔欧文），我将开发成为一个成功的，独立的调查所需的专业知识。本申请中提出的研究旨在为成瘾遗传学领域做出重大贡献，并通过利用导师的技能来帮助指导我发展独立的研究领域，从而补充我的职业发展计划。三个目的是（1）计算全基因组关联研究（GWAS）中常见SNP解释的尼古丁依赖表型方差的比例，以更好地理解数据集中可用的信息总量，（2）检查个体的同质亚组并比较个体的对比亚组，以发现与尼古丁依赖更强相关的新基因座，特别是在共病精神障碍的背景下，和（3）开发数据库以最大化发现导致尼古丁依赖的遗传变异的能力。这些研究将帮助我制定一个强大的研究计划，利用我独特的定量专业知识与临床知识的结合，更好地了解吸烟和共病精神疾病的遗传学。

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.