Pathways to Alcohol Use Disorders in ALSPAC: A Genetic-Developmental Study

描述(由申请人提供)：ALSPAC中酒精使用障碍的途径：一项遗传-发育研究酒精使用障碍(AUD)是由多种遗传和环境风险因素通过一系列复杂的发育途径产生的。很少有研究结合样本量、代表性和对所需年龄范围的足够频繁和详细的评估，从而提供一个现实的机会来理清这些复杂的病因途径。雅芳亲子纵向研究(ALSPAC)就是这样一项研究。在过去的16年里，ALSPAC项目对这一样本进行了详细的跟踪调查，首先在雅芳英格兰各地确定了13,000多名孕妇。样本现在正进入从青春期到青壮年的关键过渡期。这份申请是由弗吉尼亚联邦大学和布里斯托尔大学的一组研究人员准备的，在ALSPAC队列中有三个具体目标。第一个目标是将酒精使用和AUDS症状的详细评估添加到已经计划在18岁和20岁进行的问卷调查中。这将使我们能够捕捉到酒精使用和AUDS早期症状出现的关键发育阶段。第二个目标是进行一系列广泛的分析，试图了解酒精使用(AU)和酒精使用问题(AUP)的病因途径。这些分析的具体目标将是(1)描述青春期AU和AUPS的模式；(2)识别预测青春期AU和AUPS的儿童危险因素，并了解这些风险展开的发展过程；(3)研究这些危险因素在青春期的进一步发展及其与新出现的AU和AUPS的相互作用及其后果；(4)测试性别对与AU和AUPS相关的模式、预测因素和发展过程的调节作用；以及(5)使用在目标1下收集的18岁和20岁的数据，将AU和AUP的风险模型扩展到青壮年。这些分析将检查风险如何在三个主要领域展开：外化、内化和环境(以及这些最终如何与AU和AUP的发展相关)。这些领域中的每一个都是宽泛的，项目的目标之一将是解析这些结构并描述最相关的风险维度。该项目的第三个目标是将先前验证的一组有限风险基因的信息纳入到AIM 2中开发的AU、AUP和AUD的风险发育模型中。这将使用ALSPAC队列中至少3,000名受试者的分子遗传数据来实现，NIH不承担任何费用。这些分析将使我们能够研究生物、心理和社会过程的动态相互作用，这些过程有助于非盟和AUP的风险(和复原力)途径。由于样本量大、代表性、详细和频繁的表型评估以及基因数据的可用性，ALSPAC队列提供了一个独特的机会，在发展背景下澄清AUDS的易感性和保护性因素的复杂网络。

DESCRIPTION (provided by applicant): Pathways to Alcohol Use Disorders in ALSPAC: A Genetic-Developmental Study Alcohol Use Disorders (AUDs) emerge from diverse genetic and environmental risk factors acting through a range of complex developmental pathways. Very few studies exist that have a combination of sample size, representativeness, and sufficiently frequent and detailed assessments over the requisite age range to provide a realistic opportunity to disentangle these intricate etiologic pathways. The Avon Longitudinal Study of Parents and Children (ALSPAC) is such a study. Beginning with over 13,000 pregnant mothers ascertained around Avon England, the ALSPAC project has conducted detailed follow-ups of this sample for the last 16 years. The sample is now entering the critical transitional period from adolescence to young adulthood. This application, prepared by a team of investigators from Virginia Commonwealth University and University of Bristol, has three specific aims in the ALSPAC cohort. The first aim is to add detailed assessments of alcohol use and symptoms of AUDs to questionnaires already scheduled to occur at ages 18 and 20. This will allow us to capture a key developmental phase for alcohol use and the emergence of early symptoms of AUDs. The second aim is to conduct an extensive series of analyses seeking to understand the etiologic pathways to alcohol use (AU) and alcohol use problems (AUPs). The specific goals of these analyses will be (1) to characterize patterns of AU and AUPs across adolescence; (2) to identify childhood risk factors that predict AU and AUPs in adolescence and to understand the developmental processes by which these risks unfold; (3) to study the further development of these risk factors across adolescence and their interaction with emerging AU and its consequences; (4) to test the moderating role of gender on patterns, predictors, and developmental processes related to AU and AUPs; and (5) to extend models of risk for AU and AUPs into young adulthood using the age 18 and 20 data collected under Aim 1. The analyses will examine how risk unfolds across development across three major domains: Externalizing, Internalizing, and Environment (and how these eventually relate to AU and the development of AUPs). Each of these domains is broad, and one of the goals of the project will be to parse these constructs and delineate the most relevant risk dimensions. The third aim of the project is to incorporate information about a limited set of previously validated risk genes into developmental models of risk for AU, AUPs, and AUDs developed in Aim 2. This will be accomplished using molecular genetic data available on at least 3,000 subjects from the ALSPAC cohort at no cost to NIH. These analyses will allow us to study the dynamic interplay of biological, psychological, and social processes that contribute to pathways of risk (and resiliency) for AU and AUPs. With its large sample size, representativeness, detailed and frequent phenotypic assessments and availability of genotypic data, the ALSPAC cohort provides a unique opportunity to clarify, in a developmental context, the complex web of susceptibility and protective factors for AUDs.