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（由申请人提供）：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，她的研究兴趣集中于统计方法和计算算法的开发和应用，以了解成瘾行为的脆弱性和进展。从遗传学角度来看，该 K01 奖旨在为候选人提供实现以下目标所需的支持：(1) 更深入地了解酒精中毒及其临床表现；(2) 获得有关酒精中毒的知识；饮酒的特点艾滋病毒 感染人群；(3) 提高她在精神病学遗传学方面的熟练程度；(4) 提高她在统计建模和计算方面的技能；(5) 开发统计、遗传学和精神病学领域的独立研究计划。为了实现目标，候选人组建了一个多学科的指导团队，由一位主要导师、耶鲁大学生物统计系主任、统计遗传学、计算生物学和人类遗传学专家赵宏宇博士和三位共同导师组成： 。 Joel Gelernter 博士拥有精神疾病遗传学方面的专业知识；John Krystal 博士是应用转化神经科学方法研究酗酒的先驱；Amy Justice 博士是慢性艾滋病毒感染结果研究的专家。使用障碍是艾滋病毒感染人群中的一个主要问题。本申请中提出的研究是通过开发更好地利用纵向遗传数据的新统计方法来改进基因和基因-环境相互作用的检测。描述酒精暴露过程的特征退伍军人衰老队列研究 (VACS) 在本研究中，将开发一系列核机非参数方法并将其应用于全基因组研究，以 (1) 寻找不同级别的生物信息的联合遗传效应，例如基因、区域和途径；（2）检测影响饮酒时间模式的基因；（3）探索与酒精相关的社会环境因素（例如婚姻状况、无家可归和就业）的 G×E 相互作用。相关的问题和潜在的酒精使用过程中的 G×HIV 相互作用。新的遗传和环境相互作用的发现可能会为酒精使用障碍的病因学提供新的见解，特别是在艾滋病毒感染人群中，从拟议的研究中获得的培训和研究经验将起到重要作用。独立研究计划的基础，重点是方法学工作，以帮助了解饮酒和共病的遗传和环境机制。