Dataset Information

Circulating levels of micronutrients and risk of infections: a Mendelian randomization study.

ABSTRACT:

Background

Micronutrients play an essential role at every stage of the immune response, and deficiencies can therefore lead to increased susceptibility to infections. Previous observational studies and randomized controlled trials of micronutrients and infections are limited. We performed Mendelian randomization (MR) analyses to evaluate the effect of blood levels of eight micronutrients (copper, iron, selenium, zinc, beta-carotene, vitamin B12, vitamin C, and vitamin D) on the risk of three infections (gastrointestinal infections, pneumonia, and urinary tract infections).

Methods

Two-sample MR was conducted using publicly available summary statistics from independent cohorts of European ancestry. For the three infections, we used data from UK Biobank and FinnGen. Inverse variance-weighted MR analyses were performed, together with a range of sensitivity analyses. The threshold for statistical significance was set at P < 2.08E-03.

Results

We found a significant association between circulating levels of copper and risk of gastrointestinal infections, where a one standard deviation increase in blood levels of copper was associated with an odds ratio of gastrointestinal infections of 0.91 (95% confidence interval 0.87 to 0.97, P = 1.38E-03). This finding was robust in extensive sensitivity analyses. There was no clear association between the other micronutrients and the risk of infection.

Conclusions

Our results strongly support a role of copper in the susceptibility to gastrointestinal infections.

SUBMITTER: Flatby HM

PROVIDER: S-EPMC9993583 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Circulating levels of micronutrients and risk of infections: a Mendelian randomization study.

Flatby Helene M HM Ravi Anuradha A Damås Jan K JK Solligård Erik E Rogne Tormod T

BMC medicine 20230308 1

<h4>Background</h4>Micronutrients play an essential role at every stage of the immune response, and deficiencies can therefore lead to increased susceptibility to infections. Previous observational studies and randomized controlled trials of micronutrients and infections are limited. We performed Mendelian randomization (MR) analyses to evaluate the effect of blood levels of eight micronutrients (copper, iron, selenium, zinc, beta-carotene, vitamin B12, vitamin C, and vitamin D) on the risk of t ...[more]

PMID: 36882828

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Project description:BackgroundBenign paroxysmal positional vertigo (BPPV) is a typical vestibular disease characterized by recurrent episodes of vertigo. The role of micronutrients in BPPV pathogenesis has not been extensively studied, prompting this investigation into the relationship between circulating micronutrients and BPPV risk. This research aimed to explore the relationship between blood micronutrient levels and BPPV risk via Mendelian randomization (MR) analysis, a robust method for inferring causality from observational data.MethodsA total of 15 circulating micronutrients were assessed for their association with BPPV risk. MR analysis was conducted via the following methods: MR‒Egger, weighted median, simple model, inverse variance weighting (IVW), and weighted mode. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. A multivariate MR analysis was also conducted, incorporating potential confounders such as trauma, chronic otitis media, hearing loss, peripheral atherosclerosis, ageing, and osteoporosis.ResultsMR analysis revealed an obvious association between selenium and BPPV risk (OR 1.074, 95 % CI 1.005 to 1.148; P = 0.035). Folate was negatively related (OR 0.694, 95 % CI 0.501 to 0.962, P = 0.028) but was excluded because of inconsistent OR values across methods. Sensitivity analysis supported the IVW results, and there was no evidence of significant heterogeneity among the selenium-related instrumental variables included in the study, nor was horizontal pleiotropy detected among the instrumental variables. Multivariate MR analysis confirmed that selenium was an independent risk factor for BPPV (OR 1.22, 95 % CI 1.059 to 1.406, P = 0.006), with no significant associations observed for other micronutrients or exposure factors.ConclusionThis study provides evidence that blood selenium levels are positively associated with the risk of BPPV, suggesting a potential role for selenium in the pathogenesis of this disorder. These findings are robust to various sensitivity analyses and support the use of MR analysis to identify novel risk factors for BPPV. The identification of selenium as an independent risk factor for BPPV has implications for the development of preventive strategies and targeted interventions. It is necessary to analyse the biological mechanisms of this association and determine the therapeutic value of limiting selenium intake for BPPV to provide support for the treatment of such patients.

Project description:Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between circulating micronutrient concentrations and the overall risk of LC and three LC subtypes (namely lung adenocarcinoma (LA), squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)). The instrumental variables (IVs) of 11 micronutrients (beta-carotene, calcium, copper, folate, lycopene, magnesium, phosphorus, retinol, selenium, zinc, and vitamin B6) were screened from the published genome-wide association studies (GWAS). Summary statistics related to LC and its subtypes came from the largest meta-analysis, including 29,266 cases and 56,450 controls. Inverse-variance weighted (IVW) method is used as the main MR analysis, and the sensitivity analysis is carried out to ensure the MR assumptions. This MR study found suggestive evidence that genetically predicted 6 circulating micronutrient concentrations was correlated with the risk of overall LC (odds ratio (OR): 1.394, 95% confidence interval (CI): 1.041-1.868, p = 0.026, phosphorus), LA (OR: 0.794, 95% CI: 0.634-0.995, p = 0.045, beta-carotene; OR: 0.687, 95%CI: 0.494-0.957, p = 0.026, calcium), SqCLC (OR: 0.354, 95% CI: 0.145-0.865, p = 0.023, retinol), and SCLC (OR: 1.267, 95% CI: 1.040-1.543, p = 0.019, copper; OR: 0.801, 95% CI: 0.679-0.944, p = 0.008, zinc). We found no evidence that other micronutrients are associated with the risk of overall LC or its subtypes. Our study suggested that the increase in circulating beta-carotene, calcium, retinol, and zinc concentration may reduce the risk of LC; the increase in circulating copper and phosphorus concentration may be related to the increased risk of LC. In the future, larger replication samples of LC genetic data and larger micronutrient-related GWAS will be needed to verify our findings.

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Project description:BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

Dataset Information

Circulating levels of micronutrients and risk of infections: a Mendelian randomization study.

Background

Methods

Results

Conclusions

Publications

Circulating levels of micronutrients and risk of infections: a Mendelian randomization study.

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