Association between COVID‐19 and telomere length: A bidirectional Mendelian randomization study

Huang, Danqi; Lin, Siqi; He, Junting; Wang, Qi; Zhan, Yiqiang

doi:10.1002/jmv.28008

Cited by 64 publications

(55 citation statements)

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“…Hence, telomerase activity and long leukocyte telomeres appear to be critical elements for immune homeostasis when encountering infection (Aviv 2020 a ;Cunha et al 2020 a ; Simões et al 2020 a ; Mahmoodpoor et al 2022 ) Telomerase N/A TS N/A Predictive SNP-based markers of LTL do not identify the shorter LTL, as a causal risk factor for COVID-19 susceptibility or severity. Based on the bidirectional MR analysis, aging is not a risk factor for the increased severity of COVID-19 (Jiang et al 2022 ; Huang et al 2022 ; Xu et al 2022 ) ACE2 H/S TS VEM-CVR/Inhibition RBD of SARS-CoV-2 spike protein binds to ACE2 receptor (Sepe et al 2022 ) Furin H/S TS VEM-CVR/Inhibition RBD of SARS-CoV-2 spike protein is cleaved by Furin receptor (Paulsson-Habegger et al 2021 ; Peacock et al 2021 ) TMPRSS2 H/S TS VEM-CVR/Inhibition RBD of SARS-CoV-2 spike protein is primed by TMPRSS2 receptor. RG4 can inhibit TMPRSS2 translation and block SARS-CoV-2 entry (Hoffmann et al 2020 ; Liu et al 2022 ) DPP4 H/S TS VEM-CVR/Inhibition MERS-CoV receptor “ DPP4 ” is a candidate binding target (receptor) of the SARS-CoV-2 spike protein (Gao et al 2022 ; Li et al 2020 ) LDHA/LDHB H/S TS ...…”

Section: Introductionmentioning

confidence: 99%

“…Probably, because of such concerns, some literatures tend or appear to challenge the idea of "telomerase inhibition" by suggesting the idea of "telomerase activation" as an alternative approach to confront COVID-19 (Aviv 2020 ; Simões et al 2020 ; Mahmoodpoor et al 2022 ). On the other hand, predictive SNP-based markers of LTL do not identify the shorter LTL, as a causal risk factor for COVID-19 susceptibility or severity (Jiang et al 2022 ; Huang et al 2022 ). Similarly, based on the bidirectional Mendelian randomization (MR) analysis, aging is not a risk factor for the increased severity of COVID-19 (Xu et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Valdiani

Ofoghi

2023

Biotechnol Lett

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The pandemic phase of coronavirus disease 2019 (COVID-19) appears to be over in most countries. However, the unexpected behaviour and unstable nature of coronaviruses, including temporary hiatuses, re-emergence, emergence of new variants, and changing outbreak epicentres during the COVID-19 pandemic, have been frequently reported. The mentioned trend shows the fact that in addition to vaccine development, different strategies should be considered to deal effectively with this disease, in long term. In this regard, the role of enzymes in regulating immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently attracted much attention. Moreover, several reports confirm the association of short telomeres with sever COVID-19 symptoms. This review highlights the role of several enzymes involved in telomere length (TL) regulation and explains their relevance to SARS-CoV-2 infection. Apparently, inhibition of telomere shortening (TS) through inhibition and/or activation of these enzymes could be a potential target in the treatment of COVID-19, which may also lead to a reduction in disease severity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Valdiani

Ofoghi

2023

Biotechnol Lett

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“…MR is a genetic epidemiology method that evaluates the causal association between genetically determined exposure and disease. [22][23][24]. Early access to the results of MR studies before initiating randomized controlled trials (RCTs) can save time, effort, and research funding, and allow for more informed study design [25,26].…”

Section: Introductionmentioning

confidence: 99%

Causal Association of Folic Acid Supplementary Therapy and Gastric Ulcer: A Mendelian Randomization Study

Huang

et al. 2023

Preprint

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Background. The incidence of gastric ulcer (GU) remains high worldwide with limited prevention. While promising animal experiments have suggested a potential preventive role of folic acid (FA) in the development of gastric ulcers, the lack of robust clinical evidence has hindered its widespread implementation as a preventative measure. Therefore, this research aims to determine the relationship between FA supplementation and GU genetically by Mendelian randomization (MR) approach, in order to establish a foundation for developing more effective preventative strategies for this condition. Methods. Genome-wide association studies (GWAS) investigating the association between folic acid or folate supplementation and gastric ulcers were sourced from the UK Biobank. The primary methods for Mendelian randomization analysis were the inverse variance-weighted (IVW) methods, including fixed-effect and random-effect IVW models. Other methods used to test the robustness of the results included simple model and median, weighted model and median, as well as penalized weighted median. Results. MR analysis was performed to investigate the causal effect of FA adjuvant therapy on GU. Seven single nucleotide polymorphisms (SNPs) of genetic loci associated with FA adjuvant therapy were identified. The random-effect and fixed-effect IVW models revealed that genetically predicted FA complementary therapy was significantly related to the reduction of GU risk (OR, 0.870; 95% CI, 0.826–0.917, p < 0.001; OR, 0.870; 95% CI, 0.825–0.918, p < 0.001). Similar results were also observed using simple mode (OR, 0.826; 95% CI, 0.724–0.943, p = 0.030), Weighted mode (OR, 0.828; 95% CI, 0.728–0.941, p = 0.028), simple median method (OR, 0.835; 95% CI, 0.773–0.901, p < 0.001), weighted median (OR, 0.854; 95% CI, 0.794–0.919, p < 0.001) and penalised weighted median (OR, 0.849; 95% CI, 0.789–0.914, p < 0.001). The association between FA supplementary therapy and GU was not considerably driven by any individual SNP according to the leave-one-out sensitivity analysis. Conclusions. This MR study provides evidence from a genetic perspective that FA supplementation may decrease the risk of gastric ulcer. Clinicians should prioritize the role of FA in preventing gastric ulcers among patients.

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“…Based on genetic variations randomly passed on from parents to offspring 14 , Mendelian randomization (MR) analysis has the bene t of minimizing bias and confounding factors as an approach for integrating summary data from genome-wide association studies (GWASs) 15 . Consequently, to establish a causal relationship between exposure and complex outcome components, MR analysis has gained popularity 16 and provides an alternative solution to RCTs.…”

Section: Introductionmentioning

confidence: 99%

Causal associations between type 2 diabetes mellitus and chronic hepatitis C: A bidirectional Mendelian randomization study of East Asians

Liu

2023

Preprint

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Observational studies have shown a bidirectional relationship between type 2 diabetes mellitus (T2DM) and chronic hepatitis C (CHC). However, the causal relationship remains unknown. We explored the connection between T2DM and CHC in East Asians utilizing Mendelian randomization (MR). Two-sample bidirectional MR was applied to summarized statistics from genome-wide association studies. The inverse variance-weighted method, weighted-median method, MR-Egger regression, weighted mode, simple mode, heterogeneity test, pleiotropy test, and MR-PRESSO were employed for MR analysis. Results of various methods revealed an inverse relationship between T2DM and CHC, with an odds ratio (OR) (95% confidence interval [CI]) of 0.906 (0.858–0.957; P=0.00037), 0.825 (0.732–0.931; P=0.0025), 0.882 (0.808–0.962; P=0.00484), and 0.862 (0.772–0.961; P=0.00922) from inverse variance-weighted, MR-Egger, weighted median, and weighted mode, respectively. Further, no heterogeneity or directional pleiotropy was identified in Cochran’s Q test and Egger’s intercept. In the backward MR analysis, the P-values were all not statistically significant, indicating no detectable connection between CHC and T2DM. Finally, there was no proof of a connection involving blood sugar levels, hemoglobin A1c levels, and CHC risk. This large MR analysis revealed that T2DM had an inverse relationship with CHC, while CHC had no causality with T2DM.

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Association between COVID‐19 and telomere length: A bidirectional Mendelian randomization study

Cited by 64 publications

References 54 publications

Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Causal Association of Folic Acid Supplementary Therapy and Gastric Ulcer: A Mendelian Randomization Study

Causal associations between type 2 diabetes mellitus and chronic hepatitis C: A bidirectional Mendelian randomization study of East Asians

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