Investigating Overlapping Genetic Factors and Novel Causal Genes in Autoimmune Diseases: A Transcriptome‐Wide Association and Multiomics Study

作者：Leihua Fu, Jieni Yu, Xin Wang, Zhe Chen, Jiaying Sun, Feidan Gao, Z. Zhang, Jiaping Fu, Pan Hong, Weiying Feng · 发表于：International Journal of Genomics · 年份：2025 · DOI：10.1155/ijog/9595651 · 被引用次数：5 · 研究领域：Lymphoma Diagnosis and Treatment、IL-33, ST2, and ILC Pathways、Systemic Lupus Erythematosus Research

Background: Autoimmune diseases exhibit familial clustering and co‐occurrence, suggesting the presence of shared genetic risk factors. However, the overlapping genetic factors across these diseases have yet to be fully elucidated. This study aimed to identify shared genetic factors across five autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), Sjögren’s syndrome (SS), and polymyalgia rheumatica (PMR). Methods: A blood tissue–based transcriptome‐wide association study (TWAS) was conducted to identify candidate genes. Bayesian colocalization analysis was employed to pinpoint genetic variants shared across diseases. Multiomics summary data–based Mendelian randomization (SMR) was used to identify causal risk genes, while transcriptomic analysis, gene set variation analysis (GSVA), and weighted gene coexpression network analysis (WGCNA) were applied to further investigate the functional roles of these genes. Results: The TWAS identified 78 candidate genes across the five autoimmune diseases. Bayesian colocalization analysis revealed five genes, GTF2H4, FLOT1, HCP5, IER3, and STK19, that share genetic variants across these disorders. Specifically, RA and AS shared independent variants of GTF2H4 (rs2230365 and rs147708689, respectively). HCP5 variants were shared with SS (rs1800628) and SLE (rs1150757), and rs1800628 was also identified as a shared locus in FLOT1 for SLE. SMR analysis highlighted FLOT1 as a strong causal ...