Bountress Kaitlin E, Brick Leslie A, Sheerin Christina, Grotzinger Andrew, Bustamante Daniel, Hawn Sage E, Gillespie Nathan, Kirkpatrick Robert M, Kranzler Henry, Morey Rajendra, Edenberg Howard J, Maihofer Adam X, Disner Seth, Ashley-Koch Allison, Peterson Roseann, Lori Adriana, Stein Dan J, Kimbrel Nathan, Nievergelt Caroline, Andreassen Ole A, Luykx Jurjen, Javanbakht Arash, Youssef Nagy A, Amstadter Ananda B
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, USA.
Department of Psychiatry and Human Behavior, Quantitative Sciences Program, Alpert Medical School at Brown University, USA.
Drug Alcohol Depend. 2022 May 1;234:109430. doi: 10.1016/j.drugalcdep.2022.109430. Epub 2022 Mar 28.
Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed.
We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes.
When we differentiated genetic factors for alcohol use and AUD we observed improved model fit relative to models with all alcohol-related indicators loading onto a single factor. The genetic correlations (rG) of PTSD were quite discrepant for the alcohol use and AUD factors. This was true when modeled as a three-correlated-factor model (PTSD-AUD rG:.36, p < .001; PTSD-alcohol use rG: -0.17, p < .001) and as a Bifactor model, in which the common and unique portions of alcohol phenotypes were pulled out into an AUD-specific factor (rG with PTSD:.40, p < .001), AU-specific factor (rG with PTSD: -0.57, p < .001), and a common alcohol factor (rG with PTSD:.16, NS).
These results indicate the genetic architecture of alcohol use and AUD are differentially associated with PTSD. When the portions of variance unique to alcohol use and AUD are extracted, their genetic associations with PTSD vary substantially, suggesting different genetic architectures of alcohol phenotypes in people with PTSD.
创伤后应激障碍（PTSD）与酒精使用增加及酒精使用障碍（AUD）相关，这些都具有中等程度的遗传性。研究表明，PTSD与酒精使用之间的遗传关联不同于PTSD与AUD之间的遗传关联，但需要进一步分析。
我们使用基因组结构方程模型（genomicSEM）来分析欧洲血统参与者大规模全基因组关联研究（GWAS）的汇总统计数据，以研究PTSD（诊断和重新体验症状严重程度）与一系列酒精使用和AUD表型之间的遗传关系。
当我们区分酒精使用和AUD的遗传因素时，相对于所有与酒精相关指标都加载到单一因素的模型，我们观察到模型拟合得到改善。PTSD的遗传相关性（rG）在酒精使用和AUD因素方面差异很大。当建模为三相关因素模型（PTSD - AUD rG：.36，p <.001；PTSD - 酒精使用rG： - 0.17，p <.001）和双因素模型时都是如此，在双因素模型中，酒精表型的共同部分和独特部分被提取到一个AUD特异性因素（与PTSD的rG：.40，p <.001）、AU特异性因素（与PTSD的rG： - 0.57，p <.001）和一个共同酒精因素（与PTSD的rG：.16，无显著性差异）中。
这些结果表明，酒精使用和AUD的遗传结构与PTSD的关联存在差异。当提取酒精使用和AUD特有的方差部分时，它们与PTSD的遗传关联有很大差异，这表明PTSD患者酒精表型的遗传结构不同。
