ALCOHOL USE DISORDER IN YOUNG WOMEN: GENETIC EPIDEMIOLOGY: MOAFTS WAVE 7

描述（由申请人提供）：我们建议对MOAFTS（密苏里州青少年女性双胞胎研究）年轻队列A和B（目标N=2100双胞胎访谈）进行第七波电话诊断访谈随访，并对尚未提供样本的一些参与者进行唾液样本采集（目标N=840），用于基因分型以确认接合性。MOAFTS是一项对女性同性双胞胎对（N=370对非洲裔美国人对，N=1999对欧洲人/其他人种对）的出生队列进行的前瞻性研究，这些双胞胎对从出生记录中识别出来，并在青春期（中位年龄16岁）首次评估。该项目的目标是在一个具有广泛代表性的普通人群女性双胞胎队列中，描述酗酒和相关药物使用障碍的基因-环境相互作用，重点是㈠父母酗酒及其相关双胞胎后代环境风险暴露和结果，以及㈡女性饮酒和酒精相关问题的发展和过程，以及其他药物使用和问题（特别是烟草使用和依赖），从青春期到青年期，强调遗传和环境对问题的发生和恢复的影响的前体/中介和调节因素。在最近的数据收集中，对大约3500名21-30岁的受访者进行了采访。第七波将提供对酒精和其他物质使用和问题以及近端环境暴露的进一步随访，因此大多数双胞胎都经历了酒精问题发作的最大风险期，并且样本年龄足够大，可以提供关于缓解与持续酒精问题和酗酒的预测因素的信息（目标N=700例在30岁时评估，N=1400例在28岁时评估/N=100例新发依赖病例）。我们的研究是出于这样一种担忧，即酒精和其他物质使用障碍风险的遗传传递经常发生在通常与父母酗酒相关的高风险环境暴露的背景下-包括人际冲突和离婚或从未同居，继父母的存在，童年攻击性创伤，家庭的社会经济不利因素-酗酒的父母离开家庭并不一定会降低这种风险。通过完成第七波数据收集和数据分析，我们的目标是了解这些早期环境暴露与遗传效应如何直接或通过影响饮酒和酒精问题的发生时间和共病物质使用，以及对双胞胎随后成年角色变化的影响，（早期或延迟养育;关系的形成，冲突和解散;教育完成，就业和成年同伴关系）;并确定其他变量（儿童或起病精神病理学史，其他物质使用障碍），可能会调解或缓和这些关系。目前对女性酒精使用障碍遗传流行病学的理解主要基于回顾性或动力不足的研究-MOAFTS队列将有助于填补这一空白。公共卫生相关性：年轻女性滥用酒精会造成严重的损害，包括难以形成和维持稳定的浪漫关系、生育延迟、育儿受损，以及与危险使用有关的风险。更好地了解导致青春期和青年期女性酗酒的发病和持续与缓解的风险机制，将对激励和更好地针对年轻妇女的预防和干预工作，并在某些情况下，减少其子女的风险具有重要意义。

DESCRIPTION (provided by applicant): We propose a wave seven telephone diagnostic interview follow-up of the MOAFTS (Missouri Adolescent Female Twin Study) young cohorts A and B (target N=2100 twin interviews), and for some participants who have not yet provided samples, saliva sample collection (target N=840) for genotyping for zygosity confirmation. MOAFTS is a prospective study of a birth cohort of female like-sex twin pairs (N=370 African- American pairs, N=1999 European/Other Ancestry pairs) identified from birth records and first assessed in adolescence, at median age 16. Goals of the project are to characterize, in a broadly representative general population female twin cohort, gene-environment interplay in alcoholism and associated substance use disorders, focusing on (i) parental alcoholism and its associated twin offspring environmental risk-exposures and outcomes, and (ii) the development and course of female drinking and alcohol-related problems, as well as other substance use and problems (particularly tobacco use and dependence), through adolescence into young adulthood, emphasizing precursors/mediators and moderators of genetic and environmental effects on both onset of and recovery from problems. In the most recent data-collection, interviews were completed with approximately 3500 respondents at ages 21-30. Wave seven will provide a further follow-up of alcohol and other substance use and problems, and proximal environmental exposures, so that most twins are through their period of greatest risk for onset of alcohol problems, and the sample will be old enough to be informative about the predictors of remission versus persistence of alcohol problems and heavy drinking (target N=700 assessed at age 30, N=1400 assessed at age 28/N=100 new dependence cases). Our research is motivated by the concern that the genetic transmission of risks of alcohol and other substance use disorders frequently occurs in the context of high-risk environmental exposures commonly associated with parental alcoholism - including interpersonal conflict and divorce or never-cohabitation, step-parent presence, childhood assaultive trauma, family socioeconomic disadvantage - risks that need not be reduced by the departure of an alcoholic parent from the home. Through completion of the wave seven data-collection and data-analyses, our goals are to understand how these early environmental exposures, in combination with genetic effects, influence onset and course of heavy drinking and alcohol problems, either directly, or through effects on timing of onset of alcohol use and on comorbid substance use, and effects on subsequent adult role changes of the twins (early or delayed parenting; relationship formation, conflict and dissolution; education completion, employment, and adult peer relationships); and to identify other variables (history of childhood or adolescent-onset psychopathology, other substance use disorders) that may mediate or moderate these relationships. Current understanding of the genetic epidemiology of female alcohol use disorders is based largely on either retrospective or underpowered studies - a gap that the MOAFTS cohort will help to fill. PUBLIC HEALTH RELEVANCE: Alcohol misuse by young women is associated with significant impairments including difficulties in forming and maintaining stable romantic relationships, delayed reproduction, and impaired parenting, as well as risks associated with hazardous use. Better understanding of risk-mechanisms leading to the onset and persistence versus remission of female alcohol misuse in adolescence and young adulthood will have important implications for motivating and better targeting prevention and intervention efforts for young women and, in some cases, mitigating risks to their children.