Dataset Information

Mendelian randomization reveals no causal relationship between COVID-19 susceptibility, hospitalization, or severity and epilepsy.

ABSTRACT:

Objective

Observational studies have shown an association between COVID-19 and epilepsy. However, causality remains unproven. This study aimed to investigate the causative effect of genetically predicted COVID-19 phenotypes on epilepsy risk using a two-sample Mendelian randomization (MR) analysis.

Methods

We retrieved summary-level datasets for three COVID-19 phenotypes (COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 severity) and epilepsy from the genome-wide association studies conducted by the COVID-19 Host Genetics Initiative (COVID-19 HGI) and International League Against Epilepsy (ILAE) consortium, respectively. To analyze the final results, nine MR analytic methods were utilized. The inverse-variance weighted (IVW) method was chosen as the primary approach for data analysis to evaluate the potential causal effect. Other MR analytic methods (MR-Egger regression, weighted median estimator, mode based-estimator, and MR-PRESSO) were used as a supplement to IVW to ensure the robustness of the results.

Results

The IVW approach demonstrated no causal association between any genetically predicted COVID-19 phenotype and the risk of epilepsy [COVID-19 susceptibility: odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.86-1.14, p = 0.92; COVID-19 hospitalization: OR = 1.00, 95% CI = 0.96-1.04, p = 0.95; COVID-19 severity: OR = 0.99, 95% CI = 0.96-1.01, p = 0.25]. Other MR complementary methods revealed consistent results. Additionally, no evidence for heterogeneity and horizontal pleiotropy was found.

Significance

This MR study revealed no genetically predicted causal relationship between COVID-19 phenotypes and epilepsy.

SUBMITTER: He Z

PROVIDER: S-EPMC10690698 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Mendelian randomization reveals no causal relationship between COVID-19 susceptibility, hospitalization, or severity and epilepsy.

He Zihua Z Li Yinghong Y Liu Shengyi S Li Jinmei J

Epilepsia open 20230826 4

<h4>Objective</h4>Observational studies have shown an association between COVID-19 and epilepsy. However, causality remains unproven. This study aimed to investigate the causative effect of genetically predicted COVID-19 phenotypes on epilepsy risk using a two-sample Mendelian randomization (MR) analysis.<h4>Methods</h4>We retrieved summary-level datasets for three COVID-19 phenotypes (COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 severity) and epilepsy from the genome-wide ass ...[more]

PMID: 37602490

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Project 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.

Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic.ResultsWe found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility [IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197-0.9988, p = 0.0473], severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699-1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819-1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.ConclusionsOur MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

Dataset Information

Mendelian randomization reveals no causal relationship between COVID-19 susceptibility, hospitalization, or severity and epilepsy.

Objective

Methods

Results

Significance

Publications

Mendelian randomization reveals no causal relationship between COVID-19 susceptibility, hospitalization, or severity and epilepsy.

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