Genetic Comorbidity of PTSD and Substance Use Disorders in Diverse Populations.

不同人群中 PTSD 和药物使用障碍的遗传共病。

• 批准号: 10658078
• 负责人: ANANDA B AMSTADTER
• 金额: $ 69.48万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658078
• 关键词: African; Age of Onset; Alcohol consumption; Alcohols; Cannabis; Categories; Characteristics; Clinical; Collaborations; Communities; Data; Disease; Equation; Etiology; Feeling suicidal; Genes; Genetic; Genetic Research; Genetic Risk; Genetic Techniques; Genomics; Goals; Heritability; Individual; Intervention; Latinx; Measures; Mendelian randomization; Methods; Modeling; Molecular; Nature; Nicotine; Observational Study; Opioid; Participant; Pathway interactions; Phenotype; Population; Population Heterogeneity; Post-Traumatic Stress Disorders; Prevention; Prognosis; Public Health; Randomized; Research; Risk; Sampling Studies; Science; Severities; Sex Differences; Statistical Methods; Structure; Substance Use Disorder; Symptoms; Testing; Trauma; Twin Studies; Work; alcohol use disorder; cohort; comorbidity; data acquisition; data harmonization; genetic architecture; genome wide association study; genome-wide; genomic variation; marijuana use disorder; novel; opioid use disorder; phenotypic data; physical conditioning; psychiatric genomics; psychogenetics; public health relevance; risk sharing; substance use; success; trait

ABSTRACT/PROJECT SUMMARY Substance Use Disorders (SUD, i.e., alcohol, nicotine, cannabis, opioid) and Posttraumatic Stress Disorder (PTSD) are prevalent, highly comorbid, and associated with a high public health burden. Further, the frequent co-occurrence of SUD and PTSD has clinical implications, including greater symptom severity, poorer treatment prognosis, and poor physical health, compared to either disorder alone. Thus, there is a great need to understand their etiologic underpinnings to best inform prevention and intervention efforts. SUD and PTSD are both moderately heritable, with correlated genetic risk demonstrated by twin studies. Recent advances in statistical genetics have produced multivariate methods well suited for comorbidity applications that expand upon genetic correlations to examine causality (i.e., Mendalian Randomization [MR]), and to boost power for identification of disorder-specific and shared genetic risk (i.e., genomic structural equation modeling [gSEM]). Our work thus far has focused on the genetic relationships of PTSD with alcohol use disorder (AUD), demonstrating a significant genetic correlation between PTSD and AUD (rG=.35), and finding a support for a causal effect of PTSD on AUD. While these findings provide clues for the relationships between PTSD and other common SUD, the genetic relationships between PTSD with other SUDs, especially cannabis, and opioid use disorders remain relatively unexplored. The first aim of this project is to harness the existing large GWAS samples brought together by the Psychiatric Genomics Consortium (PGC) SUD and PTSD workgroups, to characterize the genetic relationship between SUDs and PTSD using state-of-the-science statistical genetic techniques. Initial GWAS in the PTSD and SUD workgroups have largely focused on broad phenotypes that are amendable for harmonization across cohorts. Thus, there is an unfilled need for increased data acquisition and harmonization within the workgroups to allow for more nuanced scientific questions about the PTSD-SUD relationship to be answered. For example, it is unknown if the nature of the PTSD-SUD genetic relationship is influenced by trauma characteristics (i.e., age of onset, type of trauma), differs as a function of substance use versus disorder, and how genomic risk unfolds in comorbid PTSD-SUD cases. The second aim of this project is to interrogate these more nuanced scientific questions by expanding phenotyping within the PGC groups. Importantly, existing research is limited by the under-representation of individuals of African and Latinx ancestry. The third aim of this project is to increase inclusion of diverse participants within the PTSD and SUD PGC workgroups. We will determine whether Aim 1 findings extend to populations of African and Latinx ancestry by integrating three large and diverse existing studies with data on SUD, PTSD, and trauma, and build additional collaborations to increase diversity in the PGC workgroups. The overarching goal of this proposal is to understand the genetic relationships between SUD and PTSD while increasing representation of individuals of diverse ancestry in psychiatric genetics research.

摘要/项目摘要 药物使用障碍（SUD，即酒精，尼古丁，大麻，阿片类药物）和创伤后应激障碍 （PTSD）普遍存在，高度合并，并与高公共卫生负担相关。此外，频繁 SUD和PTSD的共发生具有临床意义，包括更大的症状严重程度，治疗较差 与单独的任何一种疾病相比，预后和身体健康状况不佳。因此，有很大需要理解的 他们的病因学基础是为预防和干预工作提供最大程度的信息。 SUD和PTSD都是 中等遗传性，双胞胎研究证明了相关的遗传风险。统计的最新进展 遗传学产生了非常适合合并症应用的多元方法，这些方法扩展了遗传 检查因果关系的相关性（即Mendalian随机化[MR]），并增强识别能力 疾病特异性和共同的遗传风险（即基因组结构方程建模[GSEM]）。到目前为止我们的工作 已重点介绍了PTSD与酒精使用障碍（AUD）的遗传关系，证明了重要的 PTSD和AUD之间的遗传相关性（RG = .35），并为PTSD对AUD的因果效应提供了支持。 尽管这些发现为PTSD与其他共同SUD之间的关系提供了线索，但遗传 PTSD与其他SUD之间的关系，尤其是大麻和阿片类药物使用障碍 未探索。该项目的第一个目的是利用现有的大型GWAS样品组合在一起 精神病基因组学联盟（PGC）SUD和PTSD工作组，以表征遗传关系 使用科学统计遗传技术在SUD和PTSD之间。 PTSD中的初始GWA SUD工作组主要集中在广泛的表型上 同伙。因此，在工作组中需要增加数据获取和协调的需求 为了回答有关PTSD-SUD关系的更细微的科学问题。例如， 未知PTSD-SUD遗传关系的性质是否受创伤特征的影响（即 发病年龄，创伤类型），与物质使用与疾病的关系不同，基因组风险如何 在合并症PTSD-SUD案例中展开。该项目的第二个目的是审问这些更细微的差别 科学问题通过扩大PGC组内的表型。重要的是，现有研究是有限的 通过非洲和拉丁人血统的个人代表性不足。该项目的第三个目标是 增加在PTSD和SUD PGC工作组中的不同参与者的包含。我们将确定是否 AIM 1的发现扩展到非洲和拉丁人血统的种群，通过整合三个大而多样的现有 使用SUD，PTSD和创伤的数据进行研究，并建立其他合作以增加多样性 PGC工作组。该提案的总体目标是了解SUD之间的遗传关系 和PTSD，同时增加了精神遗传学研究中各种血统个体的代表。