Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.989950/full |
| _version_ | 1811209016997576704 |
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| author | Wenchang Xu Wenchang Xu Fengjun Zhang Yingzhou Shi Yuanzhen Chen Bin Shi Gongchang Yu |
| author_facet | Wenchang Xu Wenchang Xu Fengjun Zhang Yingzhou Shi Yuanzhen Chen Bin Shi Gongchang Yu |
| author_sort | Wenchang Xu |
| collection | DOAJ |
| description | Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in COVID-19 adverse effects is unclear. To more accurately assess the effect of aging on adverse COVID-19, we conducted this bidirectional Mendelian randomization (MR) study. Epigenetic clocks and telomere length were used as biological indicators of aging. Data on epigenetic age (PhenoAge, GrimAge, Intrinsic HorvathAge, and HannumAge) were derived from an analysis of biological aging based on genome-wide association studies (GWAS) data. The telomere length data are derived from GWAS and the susceptibility and severity data are derived from the COVID-19 Host Genetics Initiative (HGI). Firstly, epigenetic age and telomere length were used as exposures, and following a screen for appropriate instrumental variables, we used random-effects inverse variance weighting (IVW) for the main analysis, and combined it with other analysis methods (e.g., MR Egger, Weighted median, simple mode, Weighted mode) and multiple sensitivity analysis (heterogeneity analysis, horizontal multiplicity analysis, “leave-one-out” analysis). For reducing false-positive rates, Bonferroni corrected significance thresholds were used. A reverse Mendelian randomization analysis was subsequently performed with COVID-19 susceptibility and severity as the exposure. The results of the MR analysis showed no significant differences in susceptibility to aging and COVID-19. It might suggest that aging is not a risk factor for COVID-19 infection (P-values are in the range of 0.05–0.94). According to the results of our analysis, we found that aging was not a risk factor for the increased severity of COVID-19 (P > 0.05). However, severe COVID-19 can cause telomere lengths to become shorter (beta = −0.01; se = 0.01; P = 0.02779). In addition to this, severe COVID-19 infection can slow the acceleration of the epigenetic clock “GrimAge” (beta = −0.24, se = 0.07, P = 0.00122), which may be related to the closely correlation of rs35081325 and COVID-19 severity. Our study provides partial evidence for the causal effects of aging on the susceptibility and severity of COVID-19. |
| first_indexed | 2024-04-12T04:31:35Z |
| format | Article |
| id | doaj.art-b5e6f5500ebe4005b9041f57a9f89a7b |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-12T04:31:35Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-b5e6f5500ebe4005b9041f57a9f89a7b2022-12-22T03:47:55ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-09-01910.3389/fmed.2022.989950989950Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization studyWenchang Xu0Wenchang Xu1Fengjun Zhang2Yingzhou Shi3Yuanzhen Chen4Bin Shi5Gongchang Yu6School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, ChinaNeck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaSchool of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, ChinaShandong Provincial Hospital, Shandong University, Jinan, ChinaNeck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaNeck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaNeck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaObservational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in COVID-19 adverse effects is unclear. To more accurately assess the effect of aging on adverse COVID-19, we conducted this bidirectional Mendelian randomization (MR) study. Epigenetic clocks and telomere length were used as biological indicators of aging. Data on epigenetic age (PhenoAge, GrimAge, Intrinsic HorvathAge, and HannumAge) were derived from an analysis of biological aging based on genome-wide association studies (GWAS) data. The telomere length data are derived from GWAS and the susceptibility and severity data are derived from the COVID-19 Host Genetics Initiative (HGI). Firstly, epigenetic age and telomere length were used as exposures, and following a screen for appropriate instrumental variables, we used random-effects inverse variance weighting (IVW) for the main analysis, and combined it with other analysis methods (e.g., MR Egger, Weighted median, simple mode, Weighted mode) and multiple sensitivity analysis (heterogeneity analysis, horizontal multiplicity analysis, “leave-one-out” analysis). For reducing false-positive rates, Bonferroni corrected significance thresholds were used. A reverse Mendelian randomization analysis was subsequently performed with COVID-19 susceptibility and severity as the exposure. The results of the MR analysis showed no significant differences in susceptibility to aging and COVID-19. It might suggest that aging is not a risk factor for COVID-19 infection (P-values are in the range of 0.05–0.94). According to the results of our analysis, we found that aging was not a risk factor for the increased severity of COVID-19 (P > 0.05). However, severe COVID-19 can cause telomere lengths to become shorter (beta = −0.01; se = 0.01; P = 0.02779). In addition to this, severe COVID-19 infection can slow the acceleration of the epigenetic clock “GrimAge” (beta = −0.24, se = 0.07, P = 0.00122), which may be related to the closely correlation of rs35081325 and COVID-19 severity. Our study provides partial evidence for the causal effects of aging on the susceptibility and severity of COVID-19.https://www.frontiersin.org/articles/10.3389/fmed.2022.989950/fullMendelian randomizationagingCOVID-19epigenetic agetelomere lengthgenome-wide association study (GWAS) |
| spellingShingle | Wenchang Xu Wenchang Xu Fengjun Zhang Yingzhou Shi Yuanzhen Chen Bin Shi Gongchang Yu Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study Frontiers in Medicine Mendelian randomization aging COVID-19 epigenetic age telomere length genome-wide association study (GWAS) |
| title | Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study |
| title_full | Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study |
| title_fullStr | Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study |
| title_full_unstemmed | Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study |
| title_short | Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study |
| title_sort | causal association of epigenetic aging and covid 19 severity and susceptibility a bidirectional mendelian randomization study |
| topic | Mendelian randomization aging COVID-19 epigenetic age telomere length genome-wide association study (GWAS) |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.989950/full |
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