Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study
Obesity, type 2 diabetes (T2D), and severe coronavirus disease 2019 (COVID-19) are closely associated. The aim of this study was to elucidate the casual and mediating relationships of human serum metabolites on the pathways from obesity/T2D to COVID-19 using Mendelian randomization (MR) techniques....
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MDPI AG
2022-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/7/598 |
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| author | Chuiguo Huang Mai Shi Hongjiang Wu Andrea O. Y. Luk Juliana C. N. Chan Ronald C. W. Ma |
| author_facet | Chuiguo Huang Mai Shi Hongjiang Wu Andrea O. Y. Luk Juliana C. N. Chan Ronald C. W. Ma |
| author_sort | Chuiguo Huang |
| collection | DOAJ |
| description | Obesity, type 2 diabetes (T2D), and severe coronavirus disease 2019 (COVID-19) are closely associated. The aim of this study was to elucidate the casual and mediating relationships of human serum metabolites on the pathways from obesity/T2D to COVID-19 using Mendelian randomization (MR) techniques. We performed two-sample MR to study the causal effects of 309 metabolites on COVID-19 severity and susceptibility, based on summary statistics from genome-wide association studies (GWAS) of metabolites (<i>n</i> = 7824), COVID-19 phenotypes (<i>n</i> = 2,586,691), and obesity (<i>n</i> = 322,154)/T2D traits (<i>n</i> = 898,130). We conducted two-sample network MR analysis to determine the mediating metabolites on the causal path from obesity/T2D to COVID-19 phenotypes. We used multivariable MR analysis (MVMR) to discover causal metabolites independent of body mass index (BMI). Our MR analysis yielded four causal metabolites that increased the risk of severe COVID-19, including 2-stearoylglycerophosphocholine (OR 2.15; 95% CI 1.48–3.11), decanoylcarnitine (OR 1.32; 95% CI 1.17–1.50), thymol sulfate (OR 1.20; 95% CI 1.10–1.30), and bradykinin-des-arg(9) (OR 1.09; 95% CI 1.05–1.13). One significant mediator, gamma-glutamyltyrosine, lay on the causal path from T2D/obesity to severe COVID-19, with 16.67% (0.64%, 32.70%) and 6.32% (1.76%, 10.87%) increased risk, respectively, per one-standard deviation increment of genetically predicted T2D and BMI. Our comprehensive MR analyses identified credible causative metabolites, mediators of T2D and obesity, and obesity-independent causative metabolites for severe COVID-19. These biomarkers provide a novel basis for mechanistic studies for risk assessment, prognostication, and therapeutic purposes in COVID-19. |
| first_indexed | 2024-03-09T06:13:52Z |
| format | Article |
| id | doaj.art-9e59358e13fb45aaac44230252a5d6bb |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T06:13:52Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-9e59358e13fb45aaac44230252a5d6bb2023-12-03T11:55:51ZengMDPI AGMetabolites2218-19892022-06-0112759810.3390/metabo12070598Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization StudyChuiguo Huang0Mai Shi1Hongjiang Wu2Andrea O. Y. Luk3Juliana C. N. Chan4Ronald C. W. Ma5Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaDepartment of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, ChinaObesity, type 2 diabetes (T2D), and severe coronavirus disease 2019 (COVID-19) are closely associated. The aim of this study was to elucidate the casual and mediating relationships of human serum metabolites on the pathways from obesity/T2D to COVID-19 using Mendelian randomization (MR) techniques. We performed two-sample MR to study the causal effects of 309 metabolites on COVID-19 severity and susceptibility, based on summary statistics from genome-wide association studies (GWAS) of metabolites (<i>n</i> = 7824), COVID-19 phenotypes (<i>n</i> = 2,586,691), and obesity (<i>n</i> = 322,154)/T2D traits (<i>n</i> = 898,130). We conducted two-sample network MR analysis to determine the mediating metabolites on the causal path from obesity/T2D to COVID-19 phenotypes. We used multivariable MR analysis (MVMR) to discover causal metabolites independent of body mass index (BMI). Our MR analysis yielded four causal metabolites that increased the risk of severe COVID-19, including 2-stearoylglycerophosphocholine (OR 2.15; 95% CI 1.48–3.11), decanoylcarnitine (OR 1.32; 95% CI 1.17–1.50), thymol sulfate (OR 1.20; 95% CI 1.10–1.30), and bradykinin-des-arg(9) (OR 1.09; 95% CI 1.05–1.13). One significant mediator, gamma-glutamyltyrosine, lay on the causal path from T2D/obesity to severe COVID-19, with 16.67% (0.64%, 32.70%) and 6.32% (1.76%, 10.87%) increased risk, respectively, per one-standard deviation increment of genetically predicted T2D and BMI. Our comprehensive MR analyses identified credible causative metabolites, mediators of T2D and obesity, and obesity-independent causative metabolites for severe COVID-19. These biomarkers provide a novel basis for mechanistic studies for risk assessment, prognostication, and therapeutic purposes in COVID-19.https://www.mdpi.com/2218-1989/12/7/598COVID-19human serum metabolitestype 2 diabetesobesityMendelian randomizationmediation analysis |
| spellingShingle | Chuiguo Huang Mai Shi Hongjiang Wu Andrea O. Y. Luk Juliana C. N. Chan Ronald C. W. Ma Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study Metabolites COVID-19 human serum metabolites type 2 diabetes obesity Mendelian randomization mediation analysis |
| title | Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study |
| title_full | Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study |
| title_fullStr | Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study |
| title_full_unstemmed | Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study |
| title_short | Human Serum Metabolites as Potential Mediators from Type 2 Diabetes and Obesity to COVID-19 Severity and Susceptibility: Evidence from Mendelian Randomization Study |
| title_sort | human serum metabolites as potential mediators from type 2 diabetes and obesity to covid 19 severity and susceptibility evidence from mendelian randomization study |
| topic | COVID-19 human serum metabolites type 2 diabetes obesity Mendelian randomization mediation analysis |
| url | https://www.mdpi.com/2218-1989/12/7/598 |
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