scholarly journals Genetically Predicted Serum Vitamin D and COVID-19: A Mendelian Randomization Study

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1080-1080
Author(s):  
Bonnie Patchen ◽  
Andrew Clark ◽  
Nathan Gaddis ◽  
Dana Hancock ◽  
Patricia Cassano
Keyword(s):  
Vitamin D ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Serum Vitamin ◽  
Uk Biobank ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Genome Wide ◽  
The Uk ◽  
Population Controls

Abstract Objectives Observational studies suggest that low vitamin D levels are associated with increased risk and severity of COVID-19 infection. We used Mendelian randomization (MR) to investigate causality of the vitamin D—COVID-19 association. Methods We constructed a biologically plausible genetic instrument for serum vitamin D based on replicated genome-wide significant variants in genes related to vitamin D metabolism, and evaluated the validity of the genetic instrument in COVID-19 risk subgroups in the UK Biobank. We then performed two sample MR using publically available summary data for the association of the genetic instrument with serum vitamin D in the UK Biobank and with COVID-19 outcomes, including infection, severe respiratory infection, and hospitalization, in the COVID-19 Host Genetics Initiative. We used the inverse-variance weighted MR method for all analyses. Results We found little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. The odds ratio per standard deviation increase in genetically predicted serum vitamin D were: 1.04 (95% confidence interval 0.92 to 1.18) for any COVID-19 infection vs. population controls, 1.05 (0.84–1.31) for hospitalized COVID-19 vs. population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 vs. population controls, 1.15 (0.99 to 1.35) for COVID-19 positive vs. COVID-19 negative and, 1.44 (0.75 to 2.78) for hospitalized COVID-19 vs. non-hospitalized COVID-19. Results were similar in analyses where the genetic instrument included all variants with genome-wide significant associations with serum vitamin D (i.e., including variants with no known relationship to vitamin D metabolism) and where the genetic instrument was for risk of vitamin D deficiency. Conclusions Our results suggest that unconfounded, long-term differences in vitamin D status do not causally affect susceptibility to and severity of COVID-19 infection. These findings are consistent with results of a recently published MR study and suggest that associations seen in observational studies may be driven by confounding. Future directions include extending this work to non-European ancestry populations and high-risk populations, for example persons with comorbid disease. Funding Sources NIDDK, NHLBI and NHGRI of the NIH.

scholarly journals Genetically predicted serum vitamin D and COVID-19: a Mendelian randomization study

2021 ◽  
Author(s):  
Bonnie K Patchen ◽  
Andrew G Clark ◽  
Dana B Hancock ◽  
Nathan Gaddis ◽  
Patricia A Cassano
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Mendelian Randomization ◽  
Serum Vitamin ◽  
Causal Effects ◽  
European Ancestry ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Genome Wide ◽  
Population Controls

ABSTRACTObjectivesTo investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection.DesignTwo-sample Mendelian randomization study.SettingSummary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analyzed results of genome-wide analyses in the COVID-19 Host Genetics Initiative.Participants17,965 COVID-19 cases including 11,085 laboratory or physician confirmed cases, 7,885 hospitalized cases, and 4,336 severe respiratory cases, and 1,370,547 controls, primarily of European ancestry.ExposuresGenetically predicted variation in serum vitamin D status, based on genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency.Main outcome measuresSusceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalization.ResultsMendelian randomization analysis, powered to detect moderate effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as proxies for serum vitamin D concentration, the odds ratio for a standard deviation increase in serum vitamin D was 1.04 (95% confidence interval 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84-1.31) for hospitalized COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative, and 1.44 (0.75 to 2.78) for hospitalized COVID-19 versus non-hospitalized COVID-19. Results were similar in analyses that used all SNPs with genome-wide significant associations with serum vitamin D (i.e., including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency.ConclusionsThese findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects, nor do they preclude potential causal effects of acute responses to therapeutic doses of vitamin D. Future directions include extension of this work to non-European ancestry populations, and high-risk populations, for example persons with comorbid disease.

scholarly journals Genetically predicted serum vitamin D and COVID-19: a Mendelian randomisation study

2021 ◽  
pp. bmjnph-2021-000255
Author(s):  
Bonnie K Patchen ◽  
Andrew G Clark ◽  
Nathan Gaddis ◽  
Dana B Hancock ◽  
Patricia A Cassano
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Serum Vitamin ◽  
Causal Effects ◽  
European Ancestry ◽  
Mendelian Randomisation ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Genome Wide ◽  
Population Controls

ObjectivesTo investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection.DesignTwo-sample Mendelian randomisation study.SettingSummary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analysed results of genome-wide analyses in the COVID-19 Host Genetics Initiative.Participants17 965 COVID-19 cases including 11 085 laboratory or physician-confirmed cases, 7885 hospitalised cases and 4336 severe respiratory cases, and 1 370 547 controls, primarily of European ancestry.ExposuresGenetically predicted variation in serum vitamin D status, instrumented by genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency.Main outcome measuresSusceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalisation.ResultsMendelian randomisation analysis, sufficiently powered to detect effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as genetic instruments for serum vitamin D concentrations, the OR per SD higher serum vitamin D was 1.04 (95% CI 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84 to 1.31) for hospitalised COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative and 1.44 (0.75 to 2.78) for hospitalised COVID-19 versus non-hospitalised COVID-19. Results were similar in analyses using SNPs with genome-wide significant associations with serum vitamin D (ie, including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency.ConclusionsThese findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects or causal effects of acute responses to therapeutic doses of vitamin D.

scholarly journals Distribution of vitamin D status in the UK: a cross-sectional analysis of UK Biobank

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e038503
Author(s):  
Liang-Yu Lin ◽  
Liam Smeeth ◽  
Sinead Langan ◽  
Charlotte Warren-Gash
Keyword(s):  
Public Health ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
The Uk

ObjectiveNo recent large studies have described the distribution of vitamin D status in the UK. Understanding the epidemiology of vitamin D deficiency is important to inform targeted public health recommendations. This study aimed to investigate the distribution of factors associated with serum vitamin D status in a large national cohort.DesignA cross-sectional study.SettingThe UK Biobank, a prospective cohort study following the health and well-being of middle-aged and older adults recruited between 2006 and 2010.ParticipantsA total of 449 943 participants aged 40–69 years with measured serum vitamin D status were eligible for the analysis. Participants completed a questionnaire about sex, age, ethnic background, vitamin D supplementation, smoking, drinking and socioeconomic status.Primary and secondary outcome measuresWe investigated the distribution of serum vitamin D status and the association between demographic factors and vitamin D deficiency or insufficiency. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level <25 nmol/L. Multivariable logistic regression was used to assess the association between demographic factors and vitamin D status.ResultsAsian (n=4297/8000, 53.7%) and black (n=2459/7046, 34.9%) participants had a higher proportion of vitamin D deficiency than white participants (n=50 920/422 907, 12%). During spring and winter, the proportion of vitamin D deficiency was higher across the UK and higher in the north than in the south. Male sex, abnormal body mass index, non-white ethnic backgrounds, smoking and being more socioeconomically deprived were associated with higher odds of vitamin D deficiency. Increasing age, taking vitamin D supplements and drinking alcohol were associated with lower odds of deficiency.ConclusionsVitamin D status varied among different ethnic groups and by season and geographical area within the UK. Taking supplements was associated with a lower risk of vitamin D deficiency. These findings support the vitamin D supplementation recommendations of Public Health England.

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 Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

scholarly journals Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4329
Author(s):  
Alexandra Povaliaeva ◽  
Viktor Bogdanov ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Larisa Dzeranova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cushing’S Disease ◽  
Serum Vitamin ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Control Group ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Free Cortisol

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Serum Vitamin D Level and Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis of Observational Studies and Randomized Control Trials

2020 ◽  
Vol 52 (05) ◽  
pp. 305-315
Author(s):  
Nasim Säidifard ◽  
Hadith Tangestani ◽  
Kurosh Djafarian ◽  
Sakineh Shab-Bidar
Keyword(s):  
Vitamin D ◽  
Observational Studies ◽  
Meta Analysis ◽  
Serum Vitamin ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Vitamin D Supplementation ◽  
Inverse Association ◽  
Serum Vitamin D ◽  
Media Thickness

AbstractIt is reported that vitamin D deficiency is associated with carotid intima-media thickness (CIMT). In addition, several randomized clinical trials (RCTs) have studied the influence of vitamin D supplement on CIMT. However, results are inconclusive. This review aimed to systematically explore the potential link of the serum vitamin D level with CIMT pooling together observational studies and RCTs. PubMed and Scopus were searched for studies published until February 13, 2018. The Fisher’s z (SE) correlation coefficient, odds ratio (OR), and mean (SD) of changes in CIMT from baseline were used to perform meta-analysis in observational studies and RCTs, respectively. To pool data, both a fixed-effects model and a random-effects model (in case of heterogeneity) were used. Heterogeneity was assessed using Cochran’s Q and I2 tests. Nineteen observational studies and 3 RCTs met inclusion criteria. The pooled correlation coefficients of 17 observational studies showed [(Fisher’s z=− 0.41, 95% CI: –0.63 to –0.19, p<0.001), I2=96.9%, p < 0.001] a significant inverse association between serum vitamin D and risk of CIMT. Pooling three risk estimates of three studies [(OR = 1.69, 95% CI: 0.74 to 3.86, p=0.209); I2=085.1%, p<0.001)] indicated no significant association between serum vitamin D status and risk of CIMT. Combining data of RCTs showed vitamin D supplementation significantly reduced CIMT [(MD: –0.034, 95% CI: –0.62 to –0.05, p=0.012), I2=16.6%, p = 0.301]. Our findings show that serum vitamin D is inversely associated with CIMT and vitamin D supplementation may reduce CMIT.

scholarly journals Association Between Vitamin D Status and Undernutrition Indices in Children: A Systematic Review and Meta-Analysis of Observational Studies

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunhua Song ◽  
Hongzhi Sun ◽  
Ben Wang ◽  
Chunli Song ◽  
Hongying Lu
Keyword(s):  
Vitamin D ◽  
Observational Studies ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Serum Vitamin ◽  
High Serum ◽  
Risk Estimate ◽  
Vitamin D Status ◽  
Serum Vitamin D

Introduction: Undernutrition, defined as stunting, wasting, and underweight, still implicates millions of infants and children worldwide. Micronutrients have pivotal effects on growth rate. The outcomes of vitamin D deficiency on undernutrition indices have stayed controversial. The object of current study is to answer this question: is there any association between vitamin D status and undernutrition indices?Methods: The international databases were used for a systematic search to identify relevant observational studies in English up to January 2021. A random-effect model was applied to combine the results of included essays.Results: Among 3,400 citations, 7 observational studies (4 cohorts and 3 cross-sectional) were eligible to enter in meta-analysis. Analysis of the lowest 8,295 children indicated that low vs. high serum level of vitamin D is directly associated with a higher risk of wasting (Summary Risk Estimate: 1.30; 95% CI: 1.04, 1.62; I2 = 0%). However, there is no significant association between vitamin status and risk of stunting (Summary Risk Estimate: 1.10; 95% CI: 0.72, 1.70; I2 = 81.6%) and underweight (Summary Risk Estimate: 1.12; 95% CI: 0.81, 1.56; I2 = 49.2%).Conclusion: When comparing low and high serum vitamin D concentration categories, there is an inverse link between vitamin D status and wasting, but no relationship with stunting as well as underweight. However, further prospective and trial studies are required to deepen our understanding of these associations.

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