Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710000, China.
Genes (Basel). 2022 Jul 27;13(8):1341. doi: 10.3390/genes13081341.
Although previous genome-wide association studies (GWASs) on post-traumatic stress disorder (PTSD) have identified multiple risk loci, how these loci confer risk of PTSD remains unclear. Through the FUSION pipeline, we integrated two human brain proteome reference datasets (ROS/MAP and Banner) with the PTSD GWAS dataset, respectively, to conduct a proteome-wide association study (PWAS) analysis. Then two transcriptome reference weights (Rnaseq and Splicing) were applied to a transcriptome-wide association study (TWAS) analysis. Finally, the PWAS and TWAS results were investigated through brain imaging analysis. In the PWAS analysis, 8 and 13 candidate genes were identified in the ROS/MAP and Banner reference weight groups, respectively. Examples included ( = 3.00 × 10) and ( = 7.07 × 10). Moreover, the TWAS also detected multiple candidate genes associated with PTSD in two different reference weight groups, including ( = 3.84 × 10), ( = 5.09 × 10), and ( = 4.81 × 10). Further comparison of the PWAS and TWAS results in different populations detected the overlapping genes: ( = 4.90 × 10, = 1.23 × 10) in the total population and ( = 4.89 × 10, = 1.41 × 10) in females. Brain imaging analysis revealed several different brain imaging phenotypes associated with and genes. Our study identified multiple candidate genes associated with PTSD in the proteome and transcriptome levels, which may provide new clues to the pathogenesis of PTSD.
尽管先前的创伤后应激障碍（PTSD）全基因组关联研究（GWAS）已经确定了多个风险位点，但这些位点如何导致 PTSD 风险仍然不清楚。通过 FUSION 管道，我们分别将两个人类大脑蛋白质组参考数据集（ROS/MAP 和 Banner）与 PTSD GWAS 数据集整合，进行了全蛋白质组关联研究（PWAS）分析。然后，我们应用了两个转录组参考权重（Rnaseq 和 Splicing）进行了转录组全关联研究（TWAS）分析。最后，通过脑成像分析研究了 PWAS 和 TWAS 的结果。在 PWAS 分析中，ROS/MAP 和 Banner 参考权重组分别确定了 8 个和 13 个候选基因。例如， ( = 3.00 × 10) 和 ( = 7.07 × 10)。此外，TWAS 还在两个不同的参考权重组中检测到了多个与 PTSD 相关的候选基因，包括 ( = 3.84 × 10)、 ( = 5.09 × 10)和 ( = 4.81 × 10)。在不同人群中对 PWAS 和 TWAS 结果的进一步比较检测到了重叠基因：总人群中的 ( = 4.90 × 10, = 1.23 × 10)和女性中的 ( = 4.89 × 10, = 1.41 × 10)。脑成像分析揭示了与 和 基因相关的几种不同的脑成像表型。我们的研究在蛋白质组和转录组水平上确定了多个与 PTSD 相关的候选基因，这可能为 PTSD 的发病机制提供新的线索。
