Genetic Influences on the Overlap Between Internalizing and Alcohol Problems

描述(由申请人提供)： 项目概述：拟议项目的主要研究目标是调查内化症状和酒精问题之间的关系。具体地说，这将需要分析性状之间共同承担的遗传和环境责任，并努力确定影响这种联系的遗传变异。该项目的一个组成部分将通过使用遗传流行病学来解决这些目标。通过研究双胞胎群体中这些特征之间的关系，有可能将变异划分为可归因于遗传和环境因素的变异。这项建议中描述的研究使用内化症状(跨越多种障碍)和酒精问题的测量方法，将解决以下问题：共同的潜在遗传责任对这些特征之间的联系的影响程度，以及这种共同责任是特定的内化表现(如严重抑郁症状或社交恐惧症的症状)所特有的，还是在内化表型中普遍存在的问题。该项目的第二个组成部分以孪生组成部分的结果为基础。利用关于内化症状和酒精滥用共同的遗传影响结构的信息，将构建一个单一的定量表型，该表型近似于一个人在内化症状和酒精滥用问题之间重叠的遗传倾向。这一表型将被用作全基因组关联研究的因变量，目的是识别与复合表型相关的遗传变异。 公共卫生相关性： 项目简介：NIAAA的研究倡议包括描绘对酒精使用和障碍的遗传和行为易感性。拟议的项目将提高对酒精使用内化途径的潜在和具体遗传影响的理解。这一信息可用于指导内在性障碍和酒精使用障碍的治疗和预防。

DESCRIPTION (provided by applicant): Project Summary: The broad research objective of the proposed project is to investigate the relationship between internalizing symptoms and alcohol problems. Specifically, this will entail an analysis of the genetic and environmental liability shared across traits and an effort to identify genetic variants influencing this association. One component of the project will address these goals through the use of genetic epidemiology. By studying the relationship between these traits in a population of twins, it is possible to partition variance into that which is attributable to genetic versus environmental factors. Using measures of internalizing symptoms (across multiple disorders) and alcohol problems, the research described in this proposal will address questions about the degree to which shared latent genetic liability influences the association between these traits, and whether that shared liability is specific to particular manifestations of internalizing (such as symptoms of major depression, or symptoms of social phobia) or is common across internalizing phenotypes. The second component of the project builds on results from the twin component. Using information about the structure of genetic influences common to internalizing symptoms and alcohol misuse, a single quantitative phenotype will be constructed that approximates an individual's genetic liability to overlap between internalizing and alcohol problems. This phenotype will be used as the dependent variable in a genome-wide association study, with the goal of identifying genetic variants associated with the composite phenotype. PUBLIC HEALTH RELEVANCE: Project Narrative: Research initiatives of the NIAAA include delineation of genetic and behavioral vulnerability to alcohol use and disorders. The proposed project will improve understanding of the latent and specific genetic influences on an internalizing pathway to alcohol use. This information can be used to guide treatment and prevention of both internalizing disorders and alcohol use disorders.