{"title":"Gastroesophageal reflux disease increases predisposition to severe COVID-19: Insights from integrated Mendelian randomization and genetic analysis.","authors":"Jingjing Pan, Jianhua Li","doi":"10.1111/ahg.12584","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue-specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized/severe 2019 coronavirus disease (COVID-19).</p><p><strong>Methods: </strong>We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD (N = 602,604) and hospitalized COVID-19 (N = 2095,324) as well as severe COVID-19 (N = 1086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD-driven molecular pathway network was constructed using extensive literature data mining to understand the molecular-level impacts of GERD on COVID-19.</p><p><strong>Results: </strong>Our results revealed a significant positive genetic correlation between GERD and both hospitalized (r<sub>g</sub> = 0.418) and severe COVID-19 (r<sub>g</sub> = 0.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID-19 outcomes, including hospitalized COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27-1.44, p = 9.17e - 12) and severe COVID-19 (OR: 1.27, 95% CI: 1.18-1.37, p = 1.20e - 05). Additionally, GERD and both COVID-19 conditions shared one genomic locus with lead-SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome-wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_p = 2.35e - 07) and rs1123573 (eQTL_p = 2.74e - 05). Molecular pathway analysis indicated that GERD might promote the progression of COVID-19 by inducting immune-activated and inflammation-related pathways.</p><p><strong>Conclusion: </strong>These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized/severe COVID-19. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID-19.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.0000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/ahg.12584","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue-specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized/severe 2019 coronavirus disease (COVID-19).
Methods: We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD (N = 602,604) and hospitalized COVID-19 (N = 2095,324) as well as severe COVID-19 (N = 1086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD-driven molecular pathway network was constructed using extensive literature data mining to understand the molecular-level impacts of GERD on COVID-19.
Results: Our results revealed a significant positive genetic correlation between GERD and both hospitalized (rg = 0.418) and severe COVID-19 (rg = 0.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID-19 outcomes, including hospitalized COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27-1.44, p = 9.17e - 12) and severe COVID-19 (OR: 1.27, 95% CI: 1.18-1.37, p = 1.20e - 05). Additionally, GERD and both COVID-19 conditions shared one genomic locus with lead-SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome-wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_p = 2.35e - 07) and rs1123573 (eQTL_p = 2.74e - 05). Molecular pathway analysis indicated that GERD might promote the progression of COVID-19 by inducting immune-activated and inflammation-related pathways.
Conclusion: These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized/severe COVID-19. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID-19.
期刊介绍：
Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible.
Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.
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