A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity
Abstract Background Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-04887-4 |
| _version_ | 1827329027277324288 |
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| author | Xiao-tong Chen Shuai Zhi Xin-yu Han Jian-wei Jiang Guang-ming Liu Shi-tao Rao |
| author_facet | Xiao-tong Chen Shuai Zhi Xin-yu Han Jian-wei Jiang Guang-ming Liu Shi-tao Rao |
| author_sort | Xiao-tong Chen |
| collection | DOAJ |
| description | Abstract Background Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. Methods We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. Results With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10–2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10–3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. Conclusions Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19. Graphical Abstract |
| first_indexed | 2024-03-07T15:26:55Z |
| format | Article |
| id | doaj.art-93f811da02144f0dbfeee40ea58f1f5a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T15:26:55Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-93f811da02144f0dbfeee40ea58f1f5a2024-03-05T16:40:41ZengBMCJournal of Translational Medicine1479-58762024-01-0122111610.1186/s12967-024-04887-4A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severityXiao-tong Chen0Shuai Zhi1Xin-yu Han2Jian-wei Jiang3Guang-ming Liu4Shi-tao Rao5Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical UniversityDepartment of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical UniversityXiamen Key Laboratory of Marine Functional Food, College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei UniversityDepartment of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical UniversityXiamen Key Laboratory of Marine Functional Food, College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei UniversityDepartment of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical UniversityAbstract Background Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. Methods We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. Results With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10–2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10–3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. Conclusions Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19. Graphical Abstracthttps://doi.org/10.1186/s12967-024-04887-4Allergic diseasesAsthmaCOVID-19 infection/severityGWAS summary statisticsMendelian randomizationMolecular mechanism |
| spellingShingle | Xiao-tong Chen Shuai Zhi Xin-yu Han Jian-wei Jiang Guang-ming Liu Shi-tao Rao A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity Journal of Translational Medicine Allergic diseases Asthma COVID-19 infection/severity GWAS summary statistics Mendelian randomization Molecular mechanism |
| title | A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity |
| title_full | A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity |
| title_fullStr | A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity |
| title_full_unstemmed | A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity |
| title_short | A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity |
| title_sort | systematic two sample and bidirectional mr process highlights a unidirectional genetic causal effect of allergic diseases on covid 19 infection severity |
| topic | Allergic diseases Asthma COVID-19 infection/severity GWAS summary statistics Mendelian randomization Molecular mechanism |
| url | https://doi.org/10.1186/s12967-024-04887-4 |
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