Dataset Information

COVID-19 susceptibility and severity for dyslipidemia: A mendelian randomization investigation.

ABSTRACT:

Background

The severe acute respiratory syndrome coronavirus in 2019 (COVID-19) is still spreading and causing deaths worldwide, which further increased the burden of chronic diseases. Dyslipidemia is a common metabolic syndrome, which is a major risk factor for cardiovascular disease. However, studies on whether there is a direct causal relationship between COVID-19 and the exacerbation of hyperlipidemia are still scarce.

Methods

Two-sample Mendelian randomization was conducted using publicly available summary statistics from independent cohorts of European ancestry. For COVID-19 and hyperlipidemia, we used data from the ieu open GWAS project database. Inverse variance-weighted, mendelian randomization Egger, weighted median, simple mode, and weighted mode mendelian randomization analyses were performed, together with a range of sensitivity analyses.

Results

There is no direct causal relationship between COVID-19 and dyslipidemia, regardless of COVID-19 severity or either dyslipidemic outcome. In combination with previous studies, the reason for the clinical outcome that COVID-19 increased the burden of dyslipidemia may be due to the exacerbation of pre-existing disease caused by COVID-19.

Conclusions

COVID-19 has no direct causal relationship with dyslipidemia.

SUBMITTER: Liang Y

PROVIDER: S-EPMC10560011 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

COVID-19 susceptibility and severity for dyslipidemia: A mendelian randomization investigation.

Liang Yi Y Liu Liang L Liang Bo B

Heliyon 20230916 9

<h4>Background</h4>The severe acute respiratory syndrome coronavirus in 2019 (COVID-19) is still spreading and causing deaths worldwide, which further increased the burden of chronic diseases. Dyslipidemia is a common metabolic syndrome, which is a major risk factor for cardiovascular disease. However, studies on whether there is a direct causal relationship between COVID-19 and the exacerbation of hyperlipidemia are still scarce.<h4>Methods</h4>Two-sample Mendelian randomization was conducted u ...[more]

PMID: 37809746

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Project description:BackgroundEpidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses.Methods and findingsWe selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10-8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10-5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10-5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null.ConclusionsIn this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.

Project description:BackgroundIncreased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity.Methods and findingsGenetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio [OR] = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency.ConclusionsIn this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.

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:BackgroundCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which since 2019 has caused over 5 million deaths to date. The pathogenicity of the virus is highly variable ranging from asymptomatic to fatal. Evidence from experimental and observational studies suggests that circulating micronutrients may affect COVID-19 outcomes.ObjectivesTo complement and inform observational studies, we investigated the associations of genetically predicted concentrations of 12 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, vitamin D, and zinc) with SARS-CoV-2 infection risk and COVID-19 severity using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 87,870 individuals of European descent with a COVID-19 diagnosis and 2,210,804 controls from the COVID-19 host genetics initiative. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsCompared to the general population, nominally significant associations were noted for higher genetically predicted vitamin B-6 (Odds ratio per standard deviation [OR SD]: 1.06; 95% confidence interval [CI]: 1.00, 1.13; p-value = 0.036) and lower magnesium concentrations (OR SD: 0.33; 95%CI: 0.11, 0.96; P = 0.042) with COVID-19 infection risk. However, the association for magnesium was not consistent in some sensitivity analyses, and sensitivity analyses could not be performed for vitamin B-6 as only two genetic instruments were available. Genetically predicted levels of calcium, folate, β-carotene, copper, iron, vitamin B-12, vitamin D, selenium, phosphorus, or zinc were not associated with the outcomes from COVID-19 disease.ConclusionThese results, though based only on genetically predicated circulating micronutrient concentrations, provide scant evidence for possible associations of micronutrients with COVID-19 outcomes.

Dataset Information

COVID-19 susceptibility and severity for dyslipidemia: A mendelian randomization investigation.

Background

Methods

Results

Conclusions

Publications

COVID-19 susceptibility and severity for dyslipidemia: A mendelian randomization investigation.

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