Gastroesophageal reflux disease increases predisposition to severe COVID-19: Insights from integrated Mendelian randomization and genetic analysis

IF 1 4区生物学 Q4 GENETICS & HEREDITY

Annals of Human Genetics Pub Date : 2024-11-12 DOI:10.1111/ahg.12584

Jingjing Pan, Jianhua Li

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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 (r_g = 0.418) and severe COVID-19 (r_g = 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.

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胃食管反流病增加了严重 COVID-19 的易感性：孟德尔随机化和遗传学综合分析的启示。

研究目的本研究旨在探讨胃食管反流病（GERD）与住院/重症2019年冠状病毒病（COVID-19）风险之间的潜在因果关系、共享基因组位点以及潜在分子通路和组织特异性表达模式：我们采用了连锁不平衡评分回归和双向孟德尔随机化（MR）分析来探讨胃食管反流病（N = 602 604）与住院COVID-19（N = 2095 324）和严重COVID-19（N = 1086 211）之间的潜在遗传关联。此外，还从共同的关键区域提取了共享基因组位点，并通过相应的共定位分析进一步证实了这一点。通过广泛的文献数据挖掘，构建了胃食管反流病驱动的分子通路网络，以了解胃食管反流病对COVID-19的分子水平影响：结果：我们的研究结果表明，胃食管反流病与住院患者（rg = 0.418）和重度 COVID-19 患者（rg = 0.314）之间存在明显的遗传正相关。此外，MR 分析表明，胃食管反流病的遗传易感性对 COVID-19 结果有单向因果效应，包括住院 COVID-19 （几率比 [OR]：1.33，95% 置信区间 [CI]：1.27-1.44，p = 9.17e - 12）和严重 COVID-19（OR：1.27，95% CI：1.18-1.37，p = 1.20e - 05）。此外，胃食管反流病和 COVID-19 两种病症都与铅-SNPs rs1011407 和 rs1123573 共享一个基因组位点，对应于转录因子 BCL11A。共定位分析进一步表明，全基因组关联研究与表达定量性状位点（eQTL）异常之间存在显著的正相关，包括rs1011407（eQTL_p = 2.35e - 07）和rs1123573（eQTL_p = 2.74e - 05）。分子通路分析表明，胃食管反流病可能通过诱导免疫激活和炎症相关通路促进 COVID-19 的进展：这些研究结果证实，由基因决定的胃食管反流病可能会增加住院/重症 COVID-19 的易感性。共同的遗传位点和潜在的分子途径为胃食管反流病与 COVID-19 之间的因果关系提供了宝贵的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Human Genetics 生物-遗传学

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

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.