The Buffering Effects of Resilience on Alcohol Use: A Phenotypic and Genotypic Investigation

项目总结 大学期间是有问题的酒精使用/酒精使用障碍(AUD)的脆弱时期。 和创伤暴露，这是AUD、创伤后应激障碍(PTSD)的跨诊断风险因素，以及 并存的创伤后应激障碍。然而，并不是所有经历过创伤事件的人都会患上这些障碍，强调 需要确定影响创伤后结果的因素。韧性已被证明可以缓冲这些影响 酒精使用问题造成的新的创伤。到目前为止，还没有现有的研究纵向检查 大学生面对新发创伤时心理弹性对酒精使用结果的缓冲作用 样本。韧性是适度可遗传的，但需要进一步的研究来检验这种遗传性。 分子方法(即全基因组复杂性状分析；GCTA)及其通过 识别与恢复力相关的个体变异(例如，全基因组关联研究；GWAS)。 恢复力还表现出与内化性和外部性障碍的遗传重叠，包括澳门氏症。 这种重叠还没有使用分子知情设计进行检查，这证明了分子遗传学 研究AUD和Resilience之间的病因重叠。拟议的研究旨在填补这些空白 使用一项来自大型城市大学的遗传信息纵向队列研究(NIAAA-R37 AA011408) 实现三个主要目标：1)研究弹性对新发生的创伤的缓冲作用 关于酒精使用表型的事件；2)检查恢复力的总体遗传力(即GCTA)，以及 确定单个变种(即GWAS)；以及3)检查弹性的总体遗传重叠 酒精使用表型、创伤后应激障碍和其他保护性因素(例如主观幸福感)，使用总风险 分析(即多基因风险得分)。研究结果将为深入了解纵向缓冲效应和 精神复原力的病因学基础以及复原力、AUD、 以及创伤后应激障碍，这将极大地促进预防和干预工作。 本提案寻求实现与导师关系协作制定的四个培训目标 团队：1)开发创伤相关表型(即AUD)的经验研究方面的专业知识；2)开发 在表型数据的纵向统计建模方面的专长；3)获得统计方面的高级培训 分子遗传数据分析方法；4)继续建立专业发展技能，将 加强我的背景，支持我发展成为一名全面的学术研究人员，以及 加强我正在进行的临床培训。建议的研究和培训目标与国家 酒精滥用和酒精中毒研究所(NIAAA)的使命，强调临床相关性和跨学科 研究。这些研究和培训目标也与NIAAA的战略目标保持一致，以“确定 酒精使用和酒精相关情况的行为和生物标志，开发和优化方法 用于评估这些标志物，并对酒精使用、滥用和相关情况建立准确的估计。

PROJECT SUMMARY The college years encompass a time of vulnerability for problematic alcohol use/alcohol use disorder (AUD) and trauma exposure, which is a transdiagnostic risk factor for AUD, posttraumatic stress disorder (PTSD), and comorbid AUD-PTSD. However, not all who experience a traumatic event develop these disorders, highlighting the need to identify factors that impact post-trauma outcomes. Resilience has been shown to buffer the effects of new onset trauma on alcohol use problems. To date, there are no existing studies longitudinally examining the buffering effects of resilience on alcohol use outcomes in the face of new onset trauma in a college-aged sample. Resilience is moderately heritable, but further research is needed to examine this heritability using molecular approaches (i.e., genome-wide complex trait analysis; GCTA) and its genetic architecture through identifying individual variants associated with resilience (i.e., genome-wide association studies; GWAS). Resilience also demonstrates genetic overlap with internalizing and externalizing disorders, including AUD. This overlap has not been examined using a molecularly informed design, warranting molecular genetic investigation of the etiologic overlap between AUD and resilience. The proposed study aims to fill these voids using a genetically informative longitudinal cohort study from a large urban university (NIAAA-R37 AA011408) to achieve three primary aims: 1) investigate the buffering effect of resilience against new onset traumatic events on alcohol use phenotypes; 2) examine the overall heritability of resilience (i.e., GCTA), as well as identify individual variants (i.e., GWAS); and 3) examine the aggregate genetic overlap of resilience with alcohol use phenotypes, PTSD, and other protective factors (e.g., subjective well-being), using aggregate risk analyses (i.e., polygenic risk scores). Study findings will provide insight into the longitudinal buffering effect and etiologic underpinnings of psychiatric resilience as well as the shared genetic risk between resilience, AUD, and PTSD, which will greatly inform prevention and intervention efforts. The present proposal seeks to meet four training goals, developed in collaboration with the mentorship team: 1) develop expertise in the empirical study of trauma-related phenotypes (i.e., AUD); 2) develop expertise in longitudinal statistical modeling of phenotypic data; 3) obtain advanced training in statistical methods for analysis of molecular genetic data; 4) continue to build professional development skills that will strengthen my background and support my development into a well-rounded academic researcher, as well as enhance my ongoing clinical training. The proposed research and training aims align well with the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) mission, emphasizing clinically relevant, transdisciplinary research. These research and training aims also align with the NIAAA Strategic Objective to “identify behavioral and biological markers of alcohol use and alcohol-related conditions, develop and optimize methods for assessing these markers, and establish precise estimates of alcohol use, misuse, and related conditions.”