Novel Methods for Longitudinal Study of Gene-Environment Interplay in Alcoholism

酒精中毒基因与环境相互作用纵向研究的新方法

• 批准号: 9267409
• 负责人: Zuoheng Wang
• 金额: $ 17.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9267409
• 关键词: Affect; Aging; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Base Sequence; Behavior; Biological; Biometry; Characteristics; Chromosome Mapping; Chronic; Clinical; Cocaine Dependence; Cohort Studies; Complex; Computational Biology; Computational algorithm; DNA; Data; Data Set; Detection; Development; Disease; Education; Employment; Environment; Environmental Risk Factor; Etiology; Future; Genes; Genetic; Genetic Enhancement; Genetic Risk; Genetic study; Genotype; Goals; HIV; HIV Infections; HIV Seropositivity; Homelessness; Human Genetics; Income; Individual; Investigation; Joints; Justice; Knowledge; Longitudinal Studies; Longitudinal cohort; Marital Status; Measurement; Measures; Medical; Mental disorders; Mentored Research Scientist Development Award; Mentors; Methodology; Methods; Modeling; Opiate Addiction; Outcomes Research; Participant; Pathogenesis; Pathway interactions; Patients; Pattern; Phenotype; Population; Preparation; Prevention; Preventive Intervention; Psychiatry; Public Health; Public Health Schools; Research; Research Personnel; Role; Sampling; Series; Statistical Methods; Statistical Models; Suggestion; Time; Training; United States; Validation; Variant; Veterans; Work; addiction; alcohol comorbidity; alcohol exposure; alcohol related problem; alcohol risk; alcohol use disorder; analytical tool; base; case control; cohort; design; experience; gene environment interaction; genetic risk factor; genetic variant; genome wide association study; genome-wide; genome-wide analysis; improved; insight; interest; multidisciplinary; novel; programs; psychogenetics; public health relevance; simulation; skills; social; statistics; translational neuroscience

 DESCRIPTION (provided by applicant): The candidate is a genetic statistician in the Department of Biostatistics at Yale School of Public Health. Her research interests focus on the development and applications of statistical methods and computational algorithms for understanding the vulnerability and progression of addiction behaviors, from a genetic perspective. This K01 Award is designed to provide the candidate with the support necessary to accomplish the following goals: (1) to establish a more in-depth understanding of alcoholism and its clinical manifestations; (2) to gain knowledge on the characteristics of alcohol use in HIV infected population; (3) to increase her proficiency in psychiatric genetics; (4) to advance her skills in statistical modeling and computation; and (5) to develop an independent research program in the interface of statistics, genetics and psychiatry. To achieve these goals, the candidate has assembled a multi-disciplinary mentoring team comprised of a primary mentor, Dr. Hongyu Zhao, Chair of the Biostatistics Department at Yale, an expert in statistical genetics, computational biology and human genetics, and three co-mentors: Dr. Joel Gelernter, who has expertise in the genetics of psychiatric disorders; Dr. John Krystal, a pioneer in the application of translational neuroscience approaches to the study of alcoholism; and Dr. Amy Justice, an expert on outcome research in chronic HIV infection. Alcohol use disorder is a predominant problem in HIV infected population. The proposed research in this application is to improve the detection of genes and gene-environment interactions by developing novel statistical methods making better use of the longitudinal genetic data. The proposed methods will be used to characterize the course of alcohol exposure in the Veterans Aging Cohort Study (VACS). In this study, a series of kernel- machine nonparametric methods will be developed and applied to a genome-wide study to (1) search for the joint genetic effects at various levels of biological information such as genes, regions and pathways; (2) detect genes affecting the temporal patterns of alcohol use; and (3) explore G×E interactions with social- environmental factors (e.g., marital status, homelessness and employment) that are well established correlated of alcohol related problems, and potential G×HIV interactions in the course of alcohol use. The novel genetic and environmental interaction findings will likely provide new insights into the etiology of alcohol use disorder, particularly in HIV infected population. The training and research experience gained from the proposed study will serve as the groundwork for an independent research program with a focus on methodological work to help understand the genetic and environmental mechanisms underlying alcohol use and comorbid disorders.

 描述（由应用程序提供）：候选人是耶鲁大学公共卫生学院生物统计学系的遗传统计学家。她的研究兴趣集中在统计方法和计算算法的开发和应用上，以理解成瘾行为的脆弱性和进步，从遗传学角度。该K01奖项旨在为候选人提供实现以下目标所需的支持：（1）对酒精中毒及其临床表现建立更深入的理解； （2）获得有关艾滋病毒中酒精使用特征的知识 感染人群； （3）提高她对精神遗传学的熟练程度； （4）提高她在统计建模和计算方面的技能； （5）在统计，遗传学和精神病学界面中制定独立研究计划。为了实现这些目标，候选人召集了一个多学科的心理团队完成了主要的心理，Yale生物统计局主席Hongyu Zhao博士是统计遗传学，计算生物学和人类遗传学的专家，以及三个共同管理者：Joel Gelernter：Joel Gelernter博士，他在心理遗传上具有专业的精神疾病遗传学;约翰·克里斯塔尔（John Krystal）博士，是转化神经科学方法在酒精中毒研究中应用的先驱；艾米·Justice博士（Amy Justice）博士，慢性艾滋病毒感染的结果研究专家。饮酒障碍是艾滋病毒感染人群中的主要问题。该应用程序中提出的研究是通过开发新的统计方法来更好地利用纵向遗传数据来改善基因和基因环境相互作用的检测。所提出的方法将用于表征退伍军人老化队列研究（VACS）中酒精暴露的过程。在这项研究中，将开发一系列的核 - 光明非参数方法，并应用于全基因组研究的研究，以（1）在各种生物学信息（例如基因，区域和途径）上搜索联合遗传效应； （2）检测影响饮酒暂时模式的基因； （3）探索与社会环境因素（例如，婚姻状况，无家可归和就业）与酒精相关的问题相关的社会环境因素（例如，婚姻状况，无家可归和就业）的相互作用，以及在酒精使用过程中潜在的G×HIV相互作用。新型的遗传和环境相互作用发现可能会为酒精使用障碍的病因提供新的见解，尤其是在HIV感染人群中。从拟议的研究中获得的培训和研究经验将作为独立研究计划的基础，着重于方法学工作，以帮助了解酒精使用和合并症的遗传和环境机制。