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

项目摘要 大学期间是酒精使用问题/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）和 合并有AUD-PTSD然而，并不是所有经历创伤事件的人都会发展这些疾病， 需要确定影响创伤后结果的因素。恢复力已被证明可以缓冲影响 酗酒问题的新创伤到目前为止，还没有现有的研究纵向检查 大学生面对新发创伤时恢复力对酒精使用结果的缓冲作用 sample.弹性是适度遗传的，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）及其遗传结构， 识别与弹性相关的个体变体（即，全基因组关联研究; GWAS）。 复原力还表明与内化和外化疾病（包括AUD）的遗传重叠。 这种重叠还没有使用分子信息设计来检查， 调查AUD和恢复力之间的病因重叠。这项研究旨在填补这些空白 使用来自一所大型城市大学的遗传信息纵向队列研究（NIAAAA-R37 AA 011408） 本研究的主要目的有三：1）探讨心理弹性对新创伤的缓冲作用 关于酒精使用表型的事件; 2）检查弹性的总体遗传力（即，GCTA），以及 识别各个变体（即，GWAS）;和3）检查弹性的总遗传重叠， 酒精使用表型、PTSD和其他保护因素（例如，主观幸福感），使用总风险 分析（即，多基因风险评分）。研究结果将有助于深入了解纵向缓冲效应， 精神弹性的病因学基础以及弹性，AUD， 和创伤后应激障碍，这将大大有助于预防和干预工作。 本建议旨在实现与导师机制合作制定的四个培训目标 团队：1）发展创伤相关表型的经验研究方面的专业知识（即，AUD）; 2）开发 在表型数据的纵向统计建模方面的专业知识; 3）获得统计方面的高级培训 分析分子遗传数据的方法; 4）继续培养专业发展技能， 加强我的背景，支持我发展成为一个全面的学术研究人员，以及 提高我正在进行的临床训练拟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，跨学科 research.这些研究和培训目标也符合NIAAA的战略目标，即“确定 酒精使用和酒精相关疾病的行为和生物标志物，开发和优化方法 以评估这些标志物，并建立酒精使用，滥用和相关条件的精确估计。

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.”