Genetic and environmental contributions to drinking milestones in youth

遗传和环境对青少年饮酒里程碑的贡献

基本信息

批准号：
8831194
负责人：
Emily Hunt Olfson
金额：
$ 2.93万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-03 至 2016-09-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8831194
关键词：
Acetaldehyde Address Adolescence Adolescent Adoption Adult Affect African American Alcohol consumption Alcohol dehydrogenase Alcohol dependence Alcohols Behavior Complex Data Development Developmental Process Diagnostic and Statistical Manual of Mental Disorders Disease Disease Progression Environment Environmental Risk Factor Enzymes Ethanol Etiology European Family Future Gene Cluster Genes Genetic Genetic Predisposition to Disease Genotype Goals Intervention Knowledge Lead Nicotine Dependence Nicotinic Receptors Onset of illness Outcome Pattern Poison Public Health Receptor Gene Research Risk Risk Factors Role Sampling Smoking Smoking Behavior Social Environment Substance Use Disorder Testing Twin Multiple Birth Twin Studies Variant Youth adolescent alcohol alcohol involvement alcohol related problem alcohol use disorder alcohol use initiation base critical developmental period critical period drinking drinking behavior early drinking effective intervention genetic variant genetics of alcoholism genome-wide insight meetings modifiable risk parental monitoring peer prevent public health relevance underage drinking

项目摘要

DESCRIPTION (provided by applicant): Alcohol use behaviors that begin in youth are important contributors to alcohol use disorders in adulthood. Large-scale studies of adults have identified specific genetic variants that are associated at a genome-wide level with substance use disorders. The extent to which these genetic variants, individually and with other risk factors, influence early drinking behaviors is not fully understood. The goal of this project is to determine whether genetic variants identified in adults impact the development of drinking milestones in youth and how important environmental risk factors modify these effects. We will use an existing longitudinal sample of European and African American youth collected through the Collaborative Study on the Genetics of Alcoholism (COGA). Our central hypothesis is that genetic variants will affect early alcohol- related problems and that environmental factors will modify this effect. Guided by strong preliminary data generated from analyses performed by the applicant, this hypothesis will be examined in two specific aims. Aim 1 will test the effect of wel-established targeted genetic variants on adolescent drinking behaviors from drinking initiation to DSM-5 alcohol use disorders. We will initially examine functional variants in the enzyme alcohol dehydrogenase (ADH) that have been shown to have a genome-wide significant effect on alcohol use disorders in adults. We will then examine variation in the CHRNA5-CHRNA3-CHRNAB4 nicotinic receptor subunit genes that is genome-wide significant for smoking behaviors, with growing evidence for an association with adult alcohol dependence. Aim 2 will then test how known environmental risk factors for early drinking behaviors modify the effect of these targeted genetic variants. We will focus on the two environments of peer drinking and parental monitoring, which have previously been shown to influence youth drinking patterns. The proposed research is significant because it is expected to provide insight into the complex etiology of early drinking behaviors. A better understanding of how specific genetic and environmental factors contribute to these early behaviors will add to our fundamental knowledge of the developmental processes that lead to alcohol use disorders. Ultimately, identification of modifiable risk factors that influence underlying genetic vulnerabilities has the potential to infom new interventions to reduce the burden of this severe disease.

描述（由申请人提供）：青年时期开始的饮酒行为是导致成年期酒精使用障碍的重要因素。对成年人的大规模研究已经确定了在全基因组水平上与药物滥用障碍相关的特定遗传变异。这些基因变异（无论是单独的还是与其他危险因素一起）对早期饮酒行为的影响程度尚不完全清楚。该项目的目标是确定成人中发现的遗传变异是否会影响青少年饮酒里程碑的发展，以及环境风险因素对这些影响的影响有多大。我们将使用通过酒精中毒遗传学合作研究 (COGA) 收集的欧洲和非裔美国青年的现有纵向样本。我们的中心假设是，遗传变异会影响早期的酒精相关问题，而环境因素会改变这种影响。在申请人进行的分析中生成的强有力的初步数据的指导下，该假设将在两个具体目标上进行检验。目标 1 将测试已确定的目标基因变异对青少年饮酒行为（从饮酒开始到 DSM-5 酒精使用障碍）的影响。我们将首先检查乙醇脱氢酶 (ADH) 的功能变异，这些变异已被证明对成人酒精使用障碍具有全基因组的显着影响。然后，我们将检查 CHRNA5-CHRNA3-CHRNAB4 烟碱受体亚基基因的变异，这些变异在全基因组范围内对吸烟行为具有重要意义，越来越多的证据表明与成人酒精依赖有关。然后，目标 2 将测试早期饮酒行为的已知环境风险因素如何改变这些目标基因变异的影响。我们将重点关注同伴饮酒和父母监督这两种环境，此前已证明这两种环境会影响青少年的饮酒模式。这项研究意义重大，因为它有望深入了解早期饮酒行为的复杂病因。更好地了解特定的遗传和环境因素如何影响这些早期行为，将增加我们对导致酒精使用障碍的发育过程的基本了解。最终，识别影响潜在遗传脆弱性的可改变风险因素有可能为新的干预措施提供信息，以减轻这种严重疾病的负担。