Luo Chen, Zhang YaJing, Feng QiFan, Yao KaiXin, Zheng LeiLei, Yang Ye, Zheng WenXin, Li Feng, Lv YongQiang, Cai Yue
Department of Biochemistry and Molecular Biology, Basic Medical College, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, China.
Department of Anesthesiology, Shanxi Hospital Affiliated to Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China.
Sci Rep. 2024 Dec 3;14(1):30096. doi: 10.1038/s41598-024-79906-x.
Atopic dermatitis (AD) is an immune-related skin disease with a genetic background. Numerous loci have been identified associated with AD to better comprehend its complicated genetic mechanisms by genome‑wide association studies (GWASs). However, current studies reveal the underlying mechanisms of these loci in the pathogenesis of AD inadequately. Therefore, we integrated the GWAS statistics of AD with plasma proteins to explore candidate proteins correlated with the pathogenesis of AD based on protein-centered omics studies. Herein, we adopted the updated AD GWAS statistics (N = 864,982) and the dataset of plasma protein quantitative trait loci (pQTLs), comprising 1,348 proteins from individuals of European descent. We first conducted the AD-related proteome-wide association studies (PWASs) (N = 7,213) by integrating pQTLs with the AD GWAS statistics and identified twenty-six significant plasma proteins by PWAS (FDR < 0.05). Then, the potential causal proteins of AD were identified via Mendelian randomization (MR), and seventeen causal proteins of AD were discovered afterward. Following this, Bayesian colocalization analysis was then utilized to explore proteins sharing the same causal variants. Five causal proteins strongly associated with the pathogenesis of AD were eventually pinpointed. Finally, we discovered drugs that could be repurposed for AD with the plasma proteins that might contribute to the pathogenesis of AD in the Drug Gene Interaction Database.
特应性皮炎（AD）是一种具有遗传背景的免疫相关性皮肤病。通过全基因组关联研究（GWAS）已鉴定出许多与AD相关的基因座，以更好地理解其复杂的遗传机制。然而，目前的研究对这些基因座在AD发病机制中的潜在机制揭示不足。因此，我们基于以蛋白质为中心的组学研究，将AD的GWAS统计数据与血浆蛋白整合，以探索与AD发病机制相关的候选蛋白。在此，我们采用了更新后的AD GWAS统计数据（N = 864,982）和血浆蛋白定量性状基因座（pQTL）数据集，该数据集包含来自欧洲血统个体的1348种蛋白质。我们首先通过将pQTL与AD GWAS统计数据整合进行了与AD相关的全蛋白质组关联研究（PWAS）（N = 7213），并通过PWAS鉴定出26种显著的血浆蛋白（FDR < 0.05）。然后，通过孟德尔随机化（MR）鉴定AD的潜在因果蛋白，随后发现了17种AD的因果蛋白。在此之后，利用贝叶斯共定位分析来探索共享相同因果变异的蛋白质。最终确定了5种与AD发病机制密切相关的因果蛋白。最后，我们在药物基因相互作用数据库中发现了可用于AD的具有可能导致AD发病机制的血浆蛋白的药物。
