Estimating Causal Association: Internalizing and Alcohol Use Problems

描述(由申请者提供)：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内在化症状(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年)之间的因果联系。具有全国代表性的样本证实了INT和AUP之间的高共病比率，一些证据表明INT-AUP与女性的相关性可能更强。尽管它们共同发生，但先前的工作并没有完全描述这些疾病在女性发育过程中与男性相比是如何相互作用的。目前尚不清楚是否(1)INT预测AUP症状的出现(反之亦然)，(2)INT和AUP之间存在双向关系，使得各自增加对方的风险并加剧对方，以及(3)INT和AUP是导致各自的其他一般或共同原因(例如，遗传或共同环境)的后果。拟议的研究计划寻求提供证据，说明这些疾病如何从童年到成年在男性和女性中共同发展，并分离出INT对AUP的影响，而不是其他可能的共同原因的影响。该项目的数据来自三项正在进行的纵向研究：密歇根州纵向研究(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数据模拟从童年到成年的INT和AUP的共同发展，以确定与男性相比，INT对女性AUP是否有预期的影响。研究2将使用MTFS数据进行不协调的双胞胎和倾向评分分析，通过控制可能是这两种疾病的共同原因的未测量的遗传和共同的环境影响，开发关于INT对AUP的影响(反之亦然)的因果推断。研究3将使用具有全国代表性的前瞻性数据集(AddHealth)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。该项目的培训部分以Katherine Foster为PI的两个目标为中心：(1)为建立检查病因的独立调查路线而至关重要的技能方面的高级专业知识 (2)熟练掌握研究设计、统计分析和其他必要的技术技能，以便使用合理的方法解决研究问题。培训将在三年内完成，包括相关分析技术的严格课程工作，与酒精使用研究领域的杰出学者的研究合作和指导，以及科学交流领域的专业发展。根据NRSA奖项完成拟议的培训和研究，将为凯瑟琳作为一名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.