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

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.

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

BMJ Nutrition, Prevention & Health ◽

10.1136/bmjnph-2021-000255 ◽

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.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzab053_073 ◽

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.

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Vitamin D Deficiency in South Sharqiya in Oman and its Impact in ENT Patients- A Retrospective Study

Bengal Journal of Otolaryngology and Head Neck Surgery ◽

10.47210/bjohns.2016.v24i3.89 ◽

2016 ◽

Vol 24 (3) ◽

pp. 122-128

Author(s):

Hasan Abdul Cader Segana ◽

Reghunandanan Nair ◽

Fahim Ahmed Shah

Keyword(s):

Vitamin D ◽

Retrospective Study ◽

Vitamin D Deficiency ◽

Clinical Manifestations ◽

Serum Vitamin ◽

Vitamin D Supplementation ◽

Socioeconomic Background ◽

Vitamin D Metabolism ◽

Serum Vitamin D ◽

Vitamin D Levels

Introduction Vitamin D deficiency has multitude of causes and can present with varying clinical manifestations. Studies show that it can lead on to recurrent respiratory infections, ear infections and deafness. Vitamin D also has immunomodulant action. Here we discuss the varying features concerning an Otolaryngologist in general as far as Vitamin D metabolism is concerned. Materials and Methods This retrospective study was performed on 800 patients 152 males and 648 females of different socioeconomic background at secondary level regional referral hospital under Ministry of Health in Sultanate of Oman. The patients attending the outpatient clinic with various complaints and not responding to conventional treatment were advised for assessment of vitamin D [25 (OH) D] level in blood. The patients were evaluated with general history, blood samples of serum calcium, phosphate, alkaline phosphatase and serum vitamin D level were measured by the most standardized laboratory of the country. Results Out of 800 patients, 275 cases had Vitamin D levels below 20 ng/ml and 167 patients had values greater than 30 ng/ml in serum.81% patients with vitamin D deficiency were females.56.25% patients were between third and sixth decade. Otolaryngologic manifestations were acute and recurrent URTI (n=352) 44%. 7% of the patients presented with recurrent ear infection (otitis externa). The rest of them presented to a lesser extent with deafness, otosclerosis. Discussion Vitamin D deficiency has been reported worldwide as one of the commonest deficiency diseases. It can lead to autoimmune dysfunctions, Beta cell dysfunction in pancreas, Multiple sclerosis, recurrent chest infections and congestive cardiac failure. Studies have shown the involvement of cochlea with sensorineural hearing loss and otosclerosis. Conclusion Vitamin D deficiency has multi system implications as patients presenting with different signs and symptoms. Mass level screening and vitamin D supplementation should be planned to decrease its varied and multidimensional ill effects on health. Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for spectrum of disorders.

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Clinical factors correlated with vitamin D deficiency in patients with obesity scheduled for bariatric surgery: A single center experience

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000662 ◽

2020 ◽

Vol 90 (3-4) ◽

pp. 346-352

Author(s):

Vincenzo Pilone ◽

Salvatore Tramontano ◽

Carmen Cutolo ◽

Federica Marchese ◽

Antonio Maria Pagano ◽

...

Keyword(s):

Bariatric Surgery ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Inverse Correlation ◽

Model Assessment ◽

Cross Sectional ◽

Serum Vitamin D ◽

Female Sex ◽

Vitamin D Levels

Abstract. We aim to assess the prevalence of vitamin D deficiency (VDD) in patients scheduled for bariatric surgery (BS), and to identify factors that might be associated with VDD. We conducted a cross-sectional observational study involving all consecutive patients scheduled for BS from 2017 to 2019. The exclusion criteria were missing data for vitamin D levels, intake of vitamin D supplements in the 3 months prior to serum vitamin D determination, and renal insufficiency. A total of 206 patients (mean age and body mass index [BMI] of 34.9 ± 10.7 years, and 44.3 ± 6.99 kg/m2, respectively) met the inclusion criteria and were enrolled for data analysis. VDD (<19.9 ng/mL), severe VDD (<10 ng/mL), and vitamin D insufficiency (20–29.9 ng/mL) were present in 68.8 %, 12.5 %, and 31.2 % of patients, respectively. A significant inverse correlation was found between vitamin D levels and initial BMI, parathyroid hormone, and homeostatic model assessment of insulin resistance (r = −0.280, p < 0.05; r = −0.407, p = 0.038; r = −0.445, p = 0.005), respectively. VDD was significantly more prevalent in patients with higher BMI [−0.413 ± 0.12, CI95 % (−0.659; −0.167), p = 0.006], whereas no significant association between hypertension [−1.005 ± 1.65, CI95 % (−4.338; 2.326), p = 0.001], and diabetes type 2 (T2D) [−0.44 ± 2.20, CI95 % (−4.876; 3.986), p = 0.841] was found. We observed significant association between female sex and levels of vitamin D [6.69 ± 2.31, CI95 % (2.06; 11.33), p = 0.006]. The present study shows that in patients scheduled for BS, VDD deficiency is common and was associated with higher BMI, and female sex.

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SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

International Journal of Clinical and Biomedical Research ◽

10.31878/ijcbr.2019.54.05 ◽

2019 ◽

pp. 18-20

Author(s):

Sanjeeva Kumar Goud T ◽

Rahul Kunkulol

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Vitamin D3 ◽

Serum Vitamin ◽

Cross Sectional ◽

Serum Vitamin D ◽

Significant Difference ◽

Before And After

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route

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Association between vitamin D deficiency and prostate cancer: Prospective case-control study

Journal of Clinical Urology ◽

10.1177/2051415821993606 ◽

2021 ◽

pp. 205141582199360

Author(s):

Ghanshyam Kumawat ◽

Vijay Chaudhary ◽

Anurag Garg ◽

Nishkarsh Mehta ◽

Gagan Talwar ◽

...

Keyword(s):

Prostate Cancer ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Case Control Study ◽

Serum Vitamin ◽

P Value ◽

Serum Vitamin D ◽

Severe Vitamin ◽

Vitamin D Levels ◽

Control Study

Objective: We aimed to find out the association of low serum vitamin D levels with the incidence of prostate cancer through a prospective case-control study. Material and methods: This study was carried out in the tertiary care hospital (India). All newly diagnosed patients of prostate cancer and age-matched controls were included. Serum vitamin D levels were measured in all of them. Vitamin D status (ng/mL) was classified as severe deficiency <10, moderate deficiency 10–<30, normal 30–100, and toxicity >100. Normality of the data was tested by the Kolmogorov–Smirnov test, statistical analysis was done with Statistical Package for the Social Sciences version 26.0, p-value of <0.05 was considered significant. Results: In our study, 320 cases and 320 controls were included. The mean vitamin D levels in cases and controls were 15.71 ± 6.5 (ng/mL) and 17.63 ± 4.54 (ng/mL), respectively, ( p-Value <0.01). Patients with severe vitamin D deficiency (73.58%) had a Gleason score ⩾8 on biopsy and 79.24% of them had a serum prostate specific antigen (PSA) level >20 ng/mL. Conclusion: We had concluded that there was no significant association between vitamin D deficiency and increased risk of prostate cancer, although patients with higher-grade prostate cancer and with higher PSA level had severe vitamin D deficiency. Level of evidence: Not applicable for this multicentre audit.

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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

Journal of Translational Medicine ◽

10.1186/s12967-021-02973-5 ◽

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.

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Association of Vitamin D Deficiency in Newly Diagnosed Pulmonary Tuberculosis

10.53350/pjmhs2115102572 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2572-2573

Author(s):

Khalil Ullah ◽

Sajid Ur Rehman ◽

Ramsha Nadeem ◽

Muhammad Abubakar ◽

Qasim Raza

Keyword(s):

Vitamin D ◽

Pulmonary Tuberculosis ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Sampling Technique ◽

Hypovitaminosis D ◽

Control Group ◽

Sputum Smear ◽

Study Group ◽

Serum Vitamin D

Aim: Relationship between Vitamin D deficiency and pulmonary tuberculosis. Methodology: Study duration: November 2020 to April 2021 Sampling technique: A case-control study Setting: Hayatabad Medical Complex, Peshawar It included 30 adult newly identified sputum-quality pulmonary tuberculosis patients and 30 age and sex matched healthy cases as controls. All cases had undergone a thorough medical examination and repeated laboratory tests, including vitamin D, calcium, and sputum for AFB and X-ray chest. Results: Majority were males (88%). In the Study group, BMI decreased significantly i.e. 19.0 vs 23.5. Serum vitamin D concentrations were significantly lower in the tuberculosis group i.e. 17.9ng/dl than in the control group 24.8ng/dl. Mean of serum albumin in the control group was 3.9 ng/dl whereas 2.9 ng/dl in the study group. Conclusion: Hypovitaminosis D was associated with more severe medical symptoms, increased sputum smear positivity and large lesions on chest radiographs in patients with pulmonary tuberculosis. Keywords: Vitamin D, Pulmonary Tuberculosis, Sputum

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