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）与酒精使用问题（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的合并症发生率很高，一些证据表明INT-AUP的相关性在女性中可能更强。尽管它们共同发生，但之前的工作并没有完全描述这些疾病在女性与男性的发育过程中如何相互作用。目前尚不清楚(1)INT是否预示着AUP症状的发作（反之亦然），(2)INT和AUP之间存在双向关系，即每一方增加另一方的风险并加剧另一方，以及(3)INT和AUP是其他共同或一般原因（例如遗传或共同环境）导致的结果。拟议的研究项目旨在为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提供证据，并在其他可能的常见原因的影响之外，分离出INT对AUP的影响。这个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数据对从儿童期到青年期INT和AUP的共同发展进行建模，以确定与男性相比，INT是否对女性AUP有前瞻性影响。研究2将使用MTFS数据进行不一致双胞胎和倾向评分分析，通过控制未测量的遗传和共同环境影响（可能是两种疾病的共同原因），对INT对AUP的影响（反之亦然）进行因果推断。研究3将使用具有全国代表性的前瞻性数据集确定这些影响是否可复制并推广到广泛的男性和女性人群（AddHealth）。该项目的培训部分集中在PI的两个目标上，凯瑟琳·福斯特（Katherine Foster）：(1)提高技能方面的专业知识，这些技能对于建立一个独立的调查线检查病因至关重要

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.