Integrating genetic and ecological momentary assessment technologies to advance models of PTSD-AUD comorbidity

项目摘要 酒精使用障碍（AUD）和创伤后应激障碍（PTSD）通常同时发生，这种共病 与高消费、治疗退出和复发风险相关。低收入城市人口 社会经济地位尤其易患AUD和PTSD。合并AUD的病因学研究 在这些研究不足和资源不足的人群中需要PTSD，以帮助解决 知识库存在合并症的定向模型，自我药疗和易感性，尽管有 主要差距（例如，很少有研究测试因果关系的方向和/或双向性效应，缺乏特异性， 评估，缺乏性别影响测试）。此外，合并症可能受到遗传风险的影响， AUD和PTSD是中度遗传的，在潜在的遗传风险中重叠，并且在很大程度上与遗传相关。 全基因组关联研究（GWAS; rG=0.35）。黑人在遗传学研究中的代表性不足， 因此，在这一人群中进行遗传学方面的研究是非常必要的， 这方面目前的多方法研究将填补这些空白，进行遗传信息生态 使用纵向测量突发设计的瞬时评估（EMA）研究。招募的参与者 通过格雷迪创伤项目（GTP），其中包括高风险的内城居民。我们将招募样本 400人，他们将被要求提供：PTSD，AUD的临床访谈诊断数据， 共病，详细的自我报告指标，包括创伤史，健康的社会决定因素，其他风险 和保护因子，还有唾液样本来检测GWAS EMA协议将捕获时间关系 PTSD和酒精使用表型之间的关系（例如，消费，暴饮暴食，AUD症状，渴望），并澄清不 只有谁处于危险之中，但当危险行为发生时。分析将同时测试所有三种模型， 科摩罗（即，自我药疗、易感性、共担风险），并将测试性别特异性途径。以下 这是EMA的初始阶段，测量突发设计包括三个EMA突发，每个间隔两个月 此外，将发生检查随时间变化的健康社会决定因素的影响（例如，新的创伤，财务 强调，种族歧视）的功能关系，发现在第一个目标。最后，探索性目标将 进行全基因组分析，重点是一种新的多变量遗传方法，基因组结构方程 模型（gSEM），将用于产生多基因风险评分（PRS），该评分将遗传风险指数化， PTSD和AUD的共病，以及每种情况的独特风险。PRS指数化澳元- 创伤后应激障碍，独特的AUD，和独特的创伤后应激障碍，将被纳入最佳拟合模型从EMA 分析以确定所发现的表型关系是否受到遗传风险的影响。这项研究将推动 我们对共同发生的AUD和PTSD风险的理解，这对发展 有效的预防和治疗方案，特别是在种族少数的内城居民谁是 创伤暴露的风险增加，随后出现AUD和PTSD。

Project Summary Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) commonly co-occur, and this comorbidity is associated with higher consumption, treatment dropout, and risk for relapse. Urban populations of low socioeconomic status are particularly at risk for AUD and PTSD. Research on the etiology of co-occurring AUD and PTSD is needed in these understudied and low resourced populations to help address a disparity in the knowledge base. Directional models of comorbidity exist, self-medication and susceptibility, although there are major gaps (e.g., few studies testing direction of causation and or bidirectionality effects, lack of specificity of assessment, lack of test of sex effects). Additionally, comorbidity could be influenced by genetic risk as both AUD and PTSD are moderately heritable, overlap in latent genetic risk, and are genetically correlated in large genome wide association studies (GWAS; rG=0.35). Black persons are underrepresented in genetics research, and thus, genetically informed studies in this population are critically needed for equity in knowledge gained in this area. The current multi-method study will fill these gaps by conducting a genetically informative ecological momentary assessment (EMA) study using a longitudinal measurement burst design. Participants recruited through the Grady Trauma Project (GTP), which consists of high-risk inner-city residents. We will enroll a sample of 400 individuals and they will be asked to provide: clinical interview diagnostic data on PTSD, AUD, and comorbidities, detailed self-report measures including trauma history, social determinants of health, other risk and protective factors, and a saliva sample for GWAS. The EMA protocol will capture the temporal relations between PTSD and alcohol use phenotypes (e.g., consumption, binge, AUD symptoms, craving) and clarify not only who is at risk, but when the risk behaviors occur. Analyses will simultaneously test all three models of comorbidity (i.e., self-medication, susceptibility, shared risk) and will test for sex specific pathways. Following this initial period of EMA, a measurement burst design consisting of three EMA bursts, each spaced two months apart, will occur to examine the impact of time varying social determinants of health (e.g., new trauma, financial stress, racial discrimination) on the functional relationships found in the first aim. Lastly, the exploratory aim will conduct genome wide analyses with a focus on a novel multivariate genetic method, genomic Structural Equation Modeling (gSEM), which will be used to produce polygenetic risk scores (PRS) that index genetic risk for comorbidity of PTSD and AUD, and unique risk for each condition. PRS indexing shared risk between AUD- PTSD, unique to AUD, and unique to PTSD, will be incorporated into the best fitting models from the EMA analyses to determine if the phenotypic relations found are influenced by genetic risk. This study will advance our understanding of risk underlying co-occurring AUD and PTSD, which is imperative to the development of effective prevention and treatment programs, particularly among racially minoritized inner-city residents who are at increased risk for trauma exposure and subsequent AUD and PTSD.