Estimating Causal Association: Internalizing and Alcohol Use Problems

描述（由申请人提供）：拟议的培训和研究使用纵向和行为遗传学方法来调查男性和女性的内化症状（INT）和酒精使用问题（AUP;重度酒精使用和酒精使用障碍; DSM-V，美国精神病学协会，2013）之间的因果关系。具有全国代表性的样本已经证实INT和AUP之间的高共病率，并且一些证据表明INT-AUP关联在女性中可能更强。尽管它们共同出现，以前的工作还没有充分的特点，这些疾病如何相互作用，在发展过程中的妇女与男子相比。目前尚不清楚（1）INT是否预测AUP症状的发作（反之亦然），（2）INT和AUP之间存在双向关系，使得每一个都增加了另一个的风险并加剧了另一个，以及（3）INT和AUP是其他一般或常见原因的结果，这些原因导致每一个（例如，遗传学或共享环境）。拟议的研究计划旨在提供证据，说明这些疾病如何在男性和女性中从儿童期到成年期共同发展，并将INT对AUP的影响与其他可能的常见原因的影响分开。 该项目的数据来自三个正在进行的纵向研究：密歇根纵向研究（MLS），明尼苏达州双胞胎和家庭研究（MTFS）和全国青少年健康调查（AddHealth）。研究1将使用MLS数据模拟INT和AUP从儿童期到青年期的共同发展，以确定与男性相比，INT是否对女性AUP具有前瞻性影响。研究2将使用MTFS数据进行不一致的双胞胎和倾向评分分析，通过控制可能是两种疾病共同原因的未测量遗传和共享环境影响，来推断INT对AUP（反之亦然）的影响。研究3将确定这些影响是否可复制，并使用具有全国代表性的前瞻性数据集（AddHealth）推广到广泛的男性和女性人群。 该项目的培训部分集中在PI凯瑟琳福斯特的两个目标上：（1）推进技能方面的专业知识，这对于建立一个独立的调查路线检查病因学至关重要。 （2）熟练掌握研究设计、统计分析和使用合理方法解决研究问题所需的其他技术技能。培训将在三年内完成，通过相关分析技术，研究合作和指导与杰出学者在酒精使用研究领域的严格课程计划，并在科学传播领域的专业发展。完成NRSA奖励下的拟议培训和研究将为凯瑟琳作为独立研究科学家的职业生涯奠定重要基础。

DESCRIPTION (provided by applicant): The proposed training and research uses longitudinal and behavioral genetic approaches to investigate the causal link between internalizing symptoms (INT) and alcohol use problems (AUP; heavy alcohol use and alcohol use disorder; DSM-V, American Psychiatric Association, 2013) in men and women. Nationally- representative samples have confirmed high rates of comorbidity between INT and AUP and some evidence suggests that the INT-AUP association may be stronger in women. Despite their common co-occurrence, prior work has not fully characterized how these disorders interact during development in women compared with men. It remains unclear whether (1) INT predicts the onset of AUP symptoms (or vice versa), (2) a bidirectional relationship between INT and AUP is present, such that each increases risk for the other and exacerbates the other, and (3) INT and AUP are consequences of other general or common causes that contribute to each (e.g., genetics or shared environment). The proposed program of research seeks to provide evidence for how these disorders co-develop in men and women from childhood through adulthood and isolate the effects of INT on AUP over and above the influence of other possible common causes. Data for this project come from three, ongoing longitudinal studies: the Michigan Longitudinal Study (MLS), the Minnesota Twin and Family Study (MTFS), and the National Survey of Adolescent Health (AddHealth). Study 1 will model the co-development of INT and AUP from childhood through young adulthood using MLS data to determine if INT has a prospective effect on AUP in women compared with men. Study 2 will use the MTFS data to conduct discordant twin and propensity score analyses to develop causal inferences regarding the effects of INT on AUP (and vice versa) by controlling for unmeasured genetic and shared environmental influences that could be a common cause for both disorders. Study 3 will determine if these effects are replicable and generalize to a broad population of men and women using a nationally-representative prospective data set (AddHealth). The training component of the project is centered on two goals for the PI, Katherine Foster: (1) advance expertise in skills paramount for building an independent line of inquiry examining the etiological mechanisms of AUD with a focus on gender differences and (2) develop proficiency in research design, statistical analysis, and other technical skills requisite for addressing research question using sound methodology. The training will be accomplished over three years via a rigorous program of coursework in relevant analytic techniques, research collaboration and mentorship with preeminent scholars in the field of alcohol use research, and professional development in the area of scientific communication. Completion of the proposed training and research under an NRSA award would provide a vital foundation for Katherine's career as an independent research scientist.