GENETIC ARCHITECTURE OF RISK FOR ANTISOCIAL ALCOHOLISM

反社会酗酒风险的遗传结构

• 批准号: 6629533
• 负责人: SCOTT F STOLTENBERG
• 金额: $ 11.82万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6629533
• 关键词: adolescence (12-20); adult human (21+); age difference; alcoholism /alcohol abuse; amine oxidase (flavin); angers; antisocial personality; behavioral /social science research tag; behavioral genetics; clinical research; disease /disorder proneness /risk; family genetics; gender difference; genetic markers; genetic polymorphism; human subject; impulsive behavior; longitudinal human study; mathematical model; middle childhood (6-11); model design /development; preschool child (1-5); psychobiology; serotonin receptor; serotonin transporter

This is an application for a Mentored Research Scientist Development Award (K01). This award is requested to provide an opportunity for the candidate to complete a transition from basic behavior-genetic research to a clinically based program of research focused on understanding the influence of heredity on risk for antisocial alcoholism (AAL) and its comorbid disorders (CDs). The training setting is the University of Michigan Department of Psychiatry and Mental Health Research Institute. It is clear that alcoholism is not a Mendelian trait, the factors associated with its intergenerational transmission are multiple and interacting. This proposal is designed to provide the candidate with experience on several fronts, all of which will be necessary to better understand the complexities of the etiology and developmental trajectories of AAL and its CDs within a developmental systems framework. These fronts include (a) multivariate statistics, (b) molecular genetics, (c) longitudinal/developmental study designs and (d) complex adaptive systems. Implementation of these skills in the conduct of small scale research projects will position the candidate for submission of an R01 application during the award period. This application describes studies that would take place during the MRSDA period that would enable the candidate to enhance his scientific skills along each of these fronts. The major study proposed would serve to collect and archive genetic samples from 291 families participating in the University of Michigan/Michigan State University Longitudinal Study directed by Dr. Robert A. Zucker, that are well characterized phenotypically. Candidate gene analyses will be conducted to assess potential associations between genes in the serotonergic system and behavioral undercontrol in children, a risk factor for developing AAL. This sample represents an important resource to study risk for AAL and its CDs. Archiving the genetic samples will position the candidate to take advantage of expected technological advances in rapid and large-scale scoring of single nucleotide polymorphisms (SNPs) and in complexity-oriented analytic techniques. Other projects proposed include secondary analysis of a family-based genetic study data set, the development of molecular genetic markers and additional candidate gene analyses. This award would enhance the candidate's potential for developing an independent research program to study the genetics of antisocial alcoholism and its comorbid disorders.

这是指导研究科学家发展奖（K01）的申请。 要求该奖项为候选人提供一个机会，可以完成从基本行为遗传学研究到基于临床的研究计划的过渡，重点是理解遗传对反社会酒精中毒风险（AAL）及其合并症（CDS）的影响。 培训环境是密歇根大学精神病学和心理健康研究所。显然，酒精中毒不是孟德尔人的特征，其代际传播相关的因素是多重的且相互作用的。 该提案旨在为候选人提供几个方面的经验，所有这些都是为了更好地理解AAL及其在开发系统框架内的病因和发展轨迹的复杂性所必需的。 这些方面包括（a）多元统计，（b）分子遗传学，（c）纵向/发育研究设计和（d）复杂的自适应系统。 在小规模研究项目中实施这些技能将使裁决期间提交R01申请的候选人定位。该申请描述了MRSDA时期将进行的研究，这将使候选人能够在这些方面提高他的科学技能。 提出的主要研究将用于收集和存档来自密歇根大学/密歇根州立大学的291个家庭的遗传样本，由罗伯特·扎克（Robert A. 将进行候选基因分析，以评估5-羟色胺能系统中基因与儿童行为范围内的潜在关联，这是发展AAL的危险因素。 该样本代表了研究AAL及其CD风险的重要资源。 存档遗传样品将使候选人在单核苷酸多态性（SNP）的快速和大规模评分中利用预期的技术进步，并在面向复杂性的分析技术中。 提出的其他项目包括对基于家庭的遗传研究数据集的次要分析，分子遗传标记的发展和其他候选基因分析。 该奖项将增强候选人开发独立研究计划的潜力，以研究反社会酒精中毒及其合并症的遗传学。