scholarly journals An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xue Li ◽  
Jos van Geffen ◽  
Michiel van Weele ◽  
Xiaomeng Zhang ◽  
Yazhou He ◽  
...  
Keyword(s):  
Vitamin D ◽  
Respiratory Infections ◽  
Causal Effect ◽  
Vitamin D Supplementation ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Uvb Radiation ◽  
Uk Biobank ◽  
Vitamin D Levels ◽  
Weighted Median

AbstractA growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55–1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55–0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42–0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66–0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.

scholarly journals Genetically-predicted vitamin D status, ambient UVB during the pandemic and COVID-19 risk in UK Biobank: Mendelian Randomisation study

2020 ◽  
Author(s):  
Xue Li ◽  
Jos van Geffen ◽  
Michiel van Weele ◽  
Xiangrui Meng ◽  
XIAOMENG ZHANG ◽  
...  
Keyword(s):  
Vitamin D ◽  
Respiratory Infections ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Vitamin D Status ◽  
Uk Biobank ◽  
Hydroxyvitamin D ◽  
Vitamin D Levels ◽  
Mode Method ◽  
25 Hydroxyvitamin D

A growing body of evidence shows that poor vitamin D status has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes, and to explore potential causal effects. We used logistic regression to identify associations between different vitamin D variables (25-hydroxyvitamin D concentration (25-OHD), ambient UVB and genetically-predicted 25-OHD concentrations) and COVID-19 (risk of infection, hospitalisation and death) in 495,780 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to test if there was any causal effect. In total, 1,746 COVID-19 cases and 399 COVID-19 deaths occurred between March and June 2020. We found significant inverse associations between COVID-19 infection and 25-OHD in univariable models, but these associations were non-significant after adjustment for confounders. Ambient UVB was strongly and inversely associated with hospitalization and death. Although the main MR analysis showed that genetically-predicted vitamin D levels were not causally associated with COVID-19 risk, MR sensitivity analysis using weighted mode method indicated a potential causal effect (OR=0.72, 95% CI:0.53-0.98; P=0.041). In conclusion, our study found suggestive evidence of association between vitamin D and the risk or severity of COVID-19 but further studies are needed.

scholarly journals No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data

2021 ◽  
pp. bmjnph-2020-000151
Author(s):  
Hasnat A Amin ◽  
Fotios Drenos
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Causal Effect ◽  
Infection Risk ◽  
European Ancestry ◽  
Mendelian Randomisation ◽  
Upper Respiratory Tract ◽  
A Genome ◽  
Vitamin D Levels ◽  
Tract Infections

BackgroundUpper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19.MethodsWe used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity.ResultsWe found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI −0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI −0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=−0.04 (95% CI −0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=−0.24 (95% CI −0.55 to 0.08, p=0.14)).ConclusionsIn conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.

scholarly journals Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiyong Cui ◽  
Yun Tian
Keyword(s):  
Vitamin D ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Sensitivity Analyses ◽  
Global Test ◽  
Serum Vitamin D

Abstract Background The 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. Methods We 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. Results We 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. Conclusions Our 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.

scholarly journals Possible role of vitamin D supplementation in coronavirus disease 2019

2020 ◽  
Vol 6 (9) ◽  
pp. 376
Author(s):  
Devi Dayal
Keyword(s):  
Vitamin D ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Winter Season ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Vitamin D Levels ◽  
Respiratory Viral Infections ◽  
The Impact

<p>Vitamin D deficiency (VDD) is presumed to play a role in several infective and non-infective conditions such as acute respiratory infections, tuberculosis, diabetes, hypertension, stroke etc. Most of the respiratory viral infections occur during winter season when the vitamin D levels in most individuals are generally low. The current pandemic of coronavirus disease 2019 (COVID-19) which began during winter season similar to the previous epidemics due to coronaviruses, has again stirred a debate on the role of VDD in the initiation and spread of the pandemic. The data on vitamin D status in patients with COVID-19 is however lacking. Different vitamin D supplementation strategies have recently been suggested as part of several countermeasures aimed at reducing the impact of COVID-19 pandemic. This brief narrative review discusses the evidence for the link between VDD and COVID-19 and the approaches suggested for vitamin D supplementation.</p>

scholarly journals The causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

2021 ◽  
Author(s):  
Zhiyong Cui ◽  
Yun Tian
Keyword(s):  
Vitamin D ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Sensitivity Analyses ◽  
Global Test ◽  
Serum Vitamin D

AbstractBackgroundEvidence supporting the role of vitamin D in the coronavirus disease 2019 (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 median 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 therefore 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.

scholarly journals Vitamin D dan paparan sinar matahari untuk mencegah COVID-19. Fakta atau mitos ?

2020 ◽  
Vol 7 (1A) ◽  
pp. 320-328
Author(s):  
Maria Mexitalia ◽  
Martvera Susilawati ◽  
Rina Pratiwi ◽  
JC Susanto
Keyword(s):  
Vitamin D ◽  
Skin Color ◽  
Respiratory Infections ◽  
Sun Exposure ◽  
Vitamin D Supplementation ◽  
The Body ◽  
High Dose ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

Latar Belakang : Paparan sinar matahari pada kulit merupakan cara terbaik untuk sintesis vitamin D. Kadar vitamin D yang adekuat dalam tubuh merupakan proteksi terhadap berbagai penyakit seperti penyakit degeneratif, kanker dan juga infeksi saluran napas. Beberapa penelitian menghubungkan kadar vitamin D yang rendah dengan morbiditas dan mortalitas COVID-19. Hal ini menyebabkan fenomena baru pada masyarakat yaitu kebiasaan berjemur. Tujuan : Artikel ini akan membahas tentang metabolisme vitamin D, peran sinar matahari dalam mengaktifkan vitamin D di dalam tubuh, dan peran vitamin D dalam berbagai penyakit, khususnya mekanisme imunitas untuk COVID-19. Diskusi : Vitamin D meningkatkan kekebalan alami seluler terutama dengan cara menginduksi peptida antimikroba, yang meliputi cathelicidin, LL-37, 1,25-dihdroxyvitamin D dan defensins. Selain itu vitamin D akan meningkatkan sekresi hidrogen peroksida pada sel monosit. Pemberian vitamin D dosis tinggi sebanyak 10.000 IU/hari selama beberapa minggu dilanjutkan 5000 IU/hari bermanfaat untuk mencegah COVID-19, walaupun hasilnya masih memerlukan penelitian lebih lanjut. Absorpsi sinar matahari ke dalam tubuh manusia dipengaruhi oleh warna kulit, penggunaan bahan pakaian dan tabir surya , dan luas pajanan. Paparan sinar matahari sebesar satu Minimal Erythemal Dose (MED) pada orang dewasa dapat meningkatkan konsentrasi vitamin D setara dengan suplementasi 10.000 – 25.000 IU. Penelitian pada bayi yang diberi paparan 3 kali seminggu @ 5 menit pada jam 10.00-14.00, dengan paparan 50% area tubuh selama 2 bulan, mendapatkan kenaikan 25(OH)D sebesar 8,9 ng/mL. Simpulan : Vitamin D yang diaktifkan oleh paparan sinar matahari sangat bermanfaat sebagai proteksi berbagai penyakit termasuk juga pada COVID-19, walaupun efektifitasnya masih memerlukan penelitian lebih lanjut. Kata Kunci : COVID-19, vitamin D, paparan sinar matahari   Background : The exposured of sunlight on the skin is the best way for vitamin D synthesis. Adequate vitamin D levels are protection against various diseases such as degenerative diseases, cancer and also respiratory infections. Several studies have linked between low vitamin D levels with COVID-19 morbidity and mortality. This causes a new phenomenon in the community, namely sunbathing. Purpose : This review rearticle will discuss about vitamin D metabolism, the role of sunlight in activating vitamin D in the body, and the role of vitamin D in various diseases, specifically the immune mechanism for COVID-19.Discussion : Vitamin D increases cellular innate immunity mainly by inducing antimicrobial peptides, which include cathelicidin, LL-37, 1,25-dihdroxyvitamin D and defensins, and also increase the secretion of hydrogen peroxide in monocyte cells. The administration of high-dose vitamin D of 10,000 IU / day for several weeks followed by 5000 IU / day is useful to prevent COVID-19, although the results still require further research. The sun exposure to activated vitamin D body is affected by skin color, using of clothing and sunscreen, and area of ??exposure. Sun exposure of one Minimum Erythemal Dose (MED) in adults can increase vitamin D concentrations equivalent to 10,000 - 25,000 IU vitamin D supplementation. Study on infants who were given exposure 3 times a week @ 5 minutes at 10:00 to 14:00, with exposure 50% of body surface area for 2 months, increased 25(OH)D of 8.9 ng/mL. Conclusion : Vitamin D which is activated by sun exposure is very useful as protection for various diseases including COVID-19, although its effectiveness still requires further research. Keywords : vitamin D, sun exposure, COVID-19.

scholarly journals Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (6) ◽  
pp. e1003605
Author(s):  
Guillaume Butler-Laporte ◽  
Tomoko Nakanishi ◽  
Vincent Mooser ◽  
David R. Morrison ◽  
Tala Abdullah ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Severe Disease ◽  
Sensitivity Analyses ◽  
European Ancestry ◽  
Logarithmic Scale ◽  
Host Genetics ◽  
A Genome ◽  
Vitamin D Levels

Background Increased 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 findings Genetic 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. Conclusions In 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.

scholarly journals Is there an association between daytime napping and cognitive function? A Mendelian randomisation study in the UK Biobank

2021 ◽  
Author(s):  
Valentina Paz ◽  
Hassan S Dashti ◽  
Victoria Garfield
Keyword(s):  
Reaction Time ◽  
Cognitive Function ◽  
Visual Memory ◽  
Sleep Apnoea ◽  
Cognitive Outcomes ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Weighted Median ◽  
The Uk

Background: Daytime napping has been associated with cognitive function in observational studies. However, it remains elusive whether napping could be beneficial or detrimental for cognition and whether these associations are causal. Methods: Using Mendelian randomisation (MR), we studied the relationship between daytime napping and cognitive outcomes. Data were from UK Biobank (n= 378,932; mean age= 57 years). Our exposure (daytime napping) was instrumented using 92 genome-wide, independent genetic variants and our cognitive outcomes were reaction time and visual memory. Inverse-variance weighted MR was implemented, with sensitivity analyses including MR-Egger and the Weighted Median Estimator for horizontal pleiotropy. We also tested different daytime napping instruments (47 SNPs, 86 SNPs and 17 SNPs) to ensure the robustness of our results. Results: No associations were found between daytime napping and reaction time (expβ=1.01, 95%CI=1.00; 1.03), or visual memory (expβ=0.99, 95%CI=0.94; 1.05). MR-Egger and Weighted Median Estimator approaches showed no evidence of horizontal pleiotropy. Additional analyses with 47 SNPs (adjusted for excessive daytime sleepiness), 86 SNPs (excluding sleep apnoea) and 17 SNPs (no sample overlap with UKB) also showed no associations with reaction time or visual memory. Conclusions: Overall, we observed no evidence of a causal association between habitual daytime napping and reaction time and visual memory. Future studies should focus on the associations between napping and other cognitive outcomes.

Vitamin D and sleep duration: Is there a bidirectional relationship?

2020 ◽  
Vol 41 (4) ◽  
Author(s):  
Maryam Mosavat ◽  
Aisling Smyth ◽  
Diana Arabiat ◽  
Lisa Whitehead
Keyword(s):  
Vitamin D ◽  
Sleep Duration ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Bone Homeostasis ◽  
Limited Information ◽  
Physiological Processes ◽  
Vitamin D Levels ◽  
Bidirectional Relationship ◽  
Sleep Length

AbstractVitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

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