Liu Xianqiang, Li Dingchang, Gao Wenxing, Liu Hao, Chen Peng, Zhao Yingjie, Zhao Wen, Dong Guanglong
Medical School of Chinese PLA, Beijing, China.
Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Front Immunol. 2024 Nov 15;15:1442693. doi: 10.3389/fimmu.2024.1442693. eCollection 2024.
It has been reported that COVID-19 patients have an increased risk of developing IBS; however, the underlying genetic mechanisms of these associations remain largely unknown. The aim of this study was to investigate potential shared SNPs, genes, proteins, and biological pathways between COVID-19 and IBS by assessing pairwise genetic correlations and cross-trait genetic analysis.
We assessed the genetic correlation between three COVID-19 phenotypes and IBS using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods. Two different sources of IBS data were combined using METAL, and the Multi-trait analysis of GWAS (MTAG) method was applied for multi-trait analysis to enhance statistical robustness and discover new genetic associations. Independent risk loci were examined using genome-wide complex trait analysis (GCTA)-conditional and joint analysis (COJO), multi-marker analysis of genomic annotation (MAGMA), and functional mapping and annotation (FUMA), integrating various QTL information and methods to further identify risk genes and proteins. Gene set variation analysis (GSVA) was employed to compute pleiotropic gene scores, and combined with immune infiltration algorithms, IBS patients were categorized into high and low immune infiltration groups.
We found a positive genetic correlation between COVID-19 infection, COVID-19 hospitalization, and IBS. Subsequent multi-trait analysis identified nine significantly associated genomic loci. Among these, eight genetic variants were closely related to the comorbidity of IBS and COVID-19. The study also highlighted four genes and 231 proteins associated with the susceptibility to IBS identified through various analytical strategies and a stratification approach for IBS risk populations.
Our study reveals a shared genetic architecture between these two diseases, providing new insights into potential biological mechanisms and laying the groundwork for more effective interventions.
据报道，新冠病毒病（COVID-19）患者患肠易激综合征（IBS）的风险增加；然而，这些关联背后的遗传机制在很大程度上仍不清楚。本研究的目的是通过评估成对遗传相关性和跨性状遗传分析，研究COVID-19与IBS之间潜在的共享单核苷酸多态性（SNP）、基因、蛋白质和生物学途径。
我们使用连锁不平衡评分回归（LDSC）和高清似然性（HDL）方法评估了三种COVID-19表型与IBS之间的遗传相关性。使用METAL合并了两种不同来源的IBS数据，并应用全基因组关联研究的多性状分析（MTAG）方法进行多性状分析，以增强统计稳健性并发现新的遗传关联。使用全基因组复杂性状分析（GCTA）的条件和联合分析（COJO）、基因组注释的多标记分析（MAGMA）以及功能映射和注释（FUMA）来检查独立风险位点，整合各种数量性状位点（QTL）信息和方法以进一步识别风险基因和蛋白质。采用基因集变异分析（GSVA）计算多效性基因评分，并结合免疫浸润算法，将IBS患者分为高免疫浸润组和低免疫浸润组。
我们发现COVID-19感染、COVID-19住院与IBS之间存在正遗传相关性。随后的多性状分析确定了9个显著相关的基因组位点。其中，8个遗传变异与IBS和COVID-19的合并症密切相关。该研究还强调了通过各种分析策略和IBS风险人群分层方法鉴定出的与IBS易感性相关的4个基因和231种蛋白质。
我们的研究揭示了这两种疾病之间共享的遗传结构，为潜在的生物学机制提供了新见解，并为更有效的干预措施奠定了基础。
