Liwayiding Abulikemu, Maimaiti Aierpati, Pan Lin, Huang Mingrui, Yang Wenzhuo, Abudusalamu Rena
Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, No. 137, South Liyushan Road, Xinshi District, Urumqi, 830054, Xinjiang, China.
Department of Neurosurgery Central, The First Affiliated Hospital of Xinjiang Medical University, No. 137, South Liyushan Road, Xinshi District, Urumqi, 830054, Xinjiang, China.
Eur J Med Res. 2025 Jun 18;30(1):490. doi: 10.1186/s40001-025-02752-8.
A substantial body of observational evidence suggests the genetic link between autoimmune system diseases and psychiatric disorders. However, the shared genetic mechanisms remain largely unclear. This study aims to systematically explore these genetic correlations and identify potential therapeutic targets through integrative bioinformatics analyses.
We conducted a comprehensive analysis by integrating genome-wide association study (GWAS) summary data from public databases, including 15 autoimmune diseases and 8 psychiatric disorders. We examined genome-wide and regional genetic correlations and overlaps between these disorders using LDSC, HDL, LAVA, and GPA. Potential pleiotropic single nucleotide variants (SNVs) were identified through PLACO analysis. FUMA and GCTA-COJO were further used to scrutinize. In addition, MAGMA, POPS, and SMR were utilized to investigate their functions, biological mechanisms, and expression across various cell types and tissues.
Of the 120 trait pairs analyzed, 105 exhibited significant genome-wide genetic correlations or overlaps. We identified 864 pleiotropic loci and annotated 36 pleiotropic genes involved in immune response, cell activation, and signaling pathways. Notably, 11 pleiotropic genes (IL2RB, INSR, CD3G, CD247, CKB, PLCL1, STAT3, IL6R, SLAMF7, BLK, and HSPH1) were highlighted as potential therapeutic targets, reflecting their key roles in the shared genetic architecture of autoimmune and psychiatric disorders. In addition, 41 unique plasma proteins were associated with either condition.
This study provides new insights into the shared genetic landscape and biological mechanisms underlying autoimmune and psychiatric disorders. The identification of key pleiotropic genes offers promising avenues for future research and therapeutic intervention.
大量观察性证据表明自身免疫系统疾病与精神障碍之间存在遗传联系。然而，共同的遗传机制在很大程度上仍不清楚。本研究旨在通过综合生物信息学分析系统地探索这些遗传相关性并确定潜在的治疗靶点。
我们通过整合来自公共数据库的全基因组关联研究（GWAS）汇总数据进行了全面分析，包括15种自身免疫性疾病和8种精神障碍。我们使用LDSC、HDL、LAVA和GPA检查了这些疾病之间的全基因组和区域遗传相关性及重叠情况。通过PLACO分析鉴定潜在的多效性单核苷酸变异（SNV）。进一步使用FUMA和GCTA-COJO进行仔细研究。此外，利用MAGMA、POPS和SMR研究它们在各种细胞类型和组织中的功能、生物学机制及表达情况。
在分析的120对性状中，105对表现出显著的全基因组遗传相关性或重叠。我们鉴定出864个多效性位点，并注释了36个参与免疫反应、细胞活化和信号通路的多效性基因。值得注意的是，11个多效性基因（IL2RB、INSR、CD3G、CD247、CKB、PLCL1、STAT3、IL6R、SLAMF7、BLK和HSPH1）被突出为潜在的治疗靶点，反映了它们在自身免疫性和精神障碍共同遗传结构中的关键作用。此外，41种独特的血浆蛋白与这两种疾病中的任何一种相关。
本研究为自身免疫性和精神障碍潜在的共同遗传格局和生物学机制提供了新见解。关键多效性基因的鉴定为未来研究和治疗干预提供了有希望的途径。
