Association between 25 Hydroxyvitamin D Concentrations and the Risk of COVID-19: A Mendelian Randomization Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu D
PROVIDER: S-EPMC8485511 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Association between 25 Hydroxyvitamin D Concentrations and the Risk of COVID-19: A Mendelian Randomization Study.
Liu Di D Tian Qiu Yue QY Zhang Jie J Hou Hai Feng HF Li Yuan Y Wang Wei W Meng Qun Q Wang You Xin YX
Biomedical and environmental sciences : BES 20210901 9
Similar Datasets
Project description:Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consortium and the corresponding data for major depression (n = 59,851 cases and 113,154 controls) from the Psychiatric Genomics Consortium. Genetically predicted S-25OHD concentrations were not associated with major depression. The odds ratio per genetically predicted one standard deviation decrease in S-25OHD concentrations was 1.02 (95% confidence interval 0.97⁻1.08; p = 0.44). The results of this study indicate that genetically lowered S-25OHD concentrations are not associated with increased risk of developing major depression.
| S-EPMC6316636 | biostudies-literature
Project description:Circulating 25-hydroxyvitamin D (25OHD) is an appealing potential intervention for cancer risk and has been associated with oral and oropharyngeal cancer risk but evidence is inconsistent. The availability of genetic variants, uncorrelated with known confounders, but predictive of 25OHD and genetic data in a large oral and oropharyngeal cancer collaboration aids causal inference when assessing this association. A total of 5,133 oral and oropharyngeal cancer cases and 5,984 controls with genetic data were included in the study. Participants were based in Europe, North America and South America and were part of the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Five genetic variants reliably associated with circulating 25OHD were used to create a relative genetic measure of 25OHD. In the absence of measured 25OHD, two-sample Mendelian randomization using individual level outcome data were used to estimate causal odds ratios (OR) for cancer case status per standard deviation increase in log25OHD. Analyses were replicated in an independent population-based cohort (UK Biobank). In the GAME-ON study, there was little evidence of a causal association between circulating 25OHD and oral cancer (OR = 0.86 [0.68;1.09], p = 0.22), oropharyngeal cancer (OR = 1.28 [0.72;2.26], p = 0.40) or when sites were combined (OR = 1.01 [0.74;1.40], p = 0.93). Replication in UK Biobank and pooled estimates produced similar results. Our study suggests that a clinically relevant protective effect of 25OHD on oral and oropharyngeal cancer risk is unlikely and supplementation of the general population with 25OHD is unlikely to be beneficial in preventing these cancers.
| S-EPMC6099266 | biostudies-literature
Project description:BackgroundThe causal relationship between the level of serum 25-hydroxyvitamin D [25(OH)D] and the risk of erectile dysfunction (ED) is still unclear.AimWe tried to determine the causal relationship between the level of serum 25(OH)D and ED risk.MethodsIn this study, we used genome-wide association study data from the UK Biobank to analyse the relationship between serum 25(OH)D (as the exposure) and ED (as the outcome). Linkage disequilibrium score regression (LDSC) was used to assess the genetic correlation between 2 traits. The CAUSE (Causal Analysis using Summary Effect estimates) method and Mendelian randomization (MR) were employed to evaluate the bidirectional causal relationship. The MRlap method was utilized to assess the impact of sample overlap on the results. To assess potential heterogeneity and horizontal pleiotropy, we utilized methods such as MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier), weighted median, and others.OutcomesThe primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED.ResultsThe LDSC analysis did not reveal a significant genetic correlation between serum 25(OH)D and ED (rg = 0.2787, P = .3536). Additionally, the CAUSE (P value testing that the causal model is a better fit >.05) and MR analyses (odds ratio, 0.8951; 95% confidence interval, 0.7480-1.0710; P = .2260) did not support a causal relationship between 25(OH)D and ED, and our study did not detect any heterogeneity and pleiotropy.Clinical implicationsThis study provides evidence on whether vitamin D needs to be ingested to prevent or treat ED.Strengths and limitationsWe used LDSC and MR to avoid bias. However, the population in this study was limited to European ancestry.ConclusionNo causal relationship was found between 25(OH)D and ED.
| S-EPMC11411456 | biostudies-literature
Project description:Observational studies and meta-analyses have indicated a notable correlation between obesity and vitamin D deficiency, yet the causal relationship between the 2 remains contentious. This study employed a bidirectional Mendelian randomization (MR) analysis to explore the interrelation between obesity-associated body metrics: specifically body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BFP), whole-body fat percentage (WHF), and 25-hydroxyvitamin D (25(OH)D) levels. Instrumental variables for BMI, WHR, BFP, whole body fat mass (WFM), and 25(OH)D were carefully selected based on predefined thresholds. The association between these metrics and 25(OH)D levels was assessed using the TwoSampleMR package in R 4.2.3. Analysis methods included inverse variance weighted (IVW), MR Egger regression, weighted median, weighted mode, and simple mode. Sensitivity analyses were conducted employing the TwoSampleMR and MR-PRESSO software packages in R 4.2.3 to evaluate heterogeneity and multiplicity of findings. All 4 body components exhibited statistically significant causal associations with decreased 25(OH)D levels: BMI (IVW: odds ratio [OR] = 0.912, 95% confidence interval [CI]: 0.888-0.937, P < .001), WHR (IVW: OR = 0.927, 95% CI: 0.882-0.975, P = .003), BFP (IVW: OR = 0.883, 95% CI: 0.867-0.899, P < .001), and WFM (IVW: OR = 0.850, 95% CI: 0.829-0.872, P < .001). However, no statistically significant inverse causative association was observed between these body components and 25(OH)D levels. Sensitivity analyses revealed no substantial heterogeneity or pleiotropy, ensuring robustness of the findings. This study substantiates a significant causal link between 4 obesity-related body components and decreased 25(OH)D levels, excluding reverse causality.
| S-EPMC11651481 | biostudies-literature
Project description:BackgroundLow circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology.MethodsTen thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria.ResultsLower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels.ConclusionsWe found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.
| S-EPMC6819483 | biostudies-literature
Project description:BackgroundDespite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR).MethodsA two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy.ResultsThe MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP).ConclusionThe findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.
| S-EPMC10470627 | biostudies-literature
Project description:Epidemiological studies suggest that higher serum 25-hydroxyvitamin D is associated with lower risk for several cancers, including breast, prostate, colorectal, and lung cancers. To mitigate confounding, genetic instrumental variables (IVs) have been used to estimate causal associations between 25-hydroxivtamin D and cancer risk via Mendelian randomization (MR). We provide a systematic review of 31 MR studies concerning 25-hydroxyvitamin D and cancer incidence and mortality identified from biomedical databases. MR analyses were conducted almost exclusively in European-ancestry populations and identified no statistically significant associations between higher genetically predicted 25-hydroxyvitamin D and lower risk for total cancer or colorectal, breast, prostate, lung, or pancreatic cancers. In recent studies including ≥80 genetic IVs for 25-hydroxyvitamin D, null associations were reported for total cancer (odds ratio [95% confidence interval] per 1-standard deviation increase: 0.98 [0.93-1.04]), breast (1.00 [0.98-1.02]), colorectal (0.97 [0.88-1.07]), prostate (0.99 [0.98-1.01]), and lung cancer (1.00 [0.93-1.03]). A protective association was observed for ovarian cancer in the Ovarian Cancer Association Consortium (0.78 [0.63-0.96] per 20 nmol/L increase, p-trend = 0.03), but not in the UK Biobank (1.10 [0.80-1.51]). Null associations were reported for other tumor sites (bladder, endometrium, uterus, esophagus, oral cavity and pharynx, kidney, liver, thyroid, or neural cells). An inconsistent protective association for cancer-specific mortality was also observed. Results from MR analyses do not support causal associations between 25-hydroxyvitamin D and risk for cancer incidence or mortality. Studies including non-White populations may be valuable to understand low 25-hydroxyvitamin D as a modifiable risk factor in populations with a higher risk of common cancers, including African ancestry individuals.
| S-EPMC9865859 | biostudies-literature
Project description:The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the "GWAS Catalog" from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63-1.09) for total cancer and 1.00 (95% CI 0.80-1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57-1.19) for total cancer and 1.01 (95% CI 0.75-1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.
| S-EPMC9918529 | biostudies-literature
Project description:Since December 2019, COVID-19 has triggered a global pandemic. The association of COVID-19 with the long-term reproductive situation of women and males is not clear. Thus, our aim was to assess the causal association between COVID-19 and infertility using Mendelian randomization (MR) analysis based on the OpenGWAS database. Two-sample MR analysis was conducted using one genome-wide association study (GWAS) on COVID-19 and infertility in individuals of European ancestry. The summary data of genetic variation come from the GWAS in European populations. We applied several MR methods, including MR Egger, weighted median, inverse variance weighted, simple mode, weighted mode, to test causal relationships. After observing the statistical analysis results of MR, we conducted sensitivity analysis to test robustness. After gene prediction, it was found that there was no clear causal relationship between COVID-19 and male infertility in MR analysis [OR 0.4702 (95% CI, 0.1569-1.4093), P = .178]. Moreover, COVID-19 was not associated with female infertility [OR 0.9981 (95% CI, 0.763-1.544), P = .646]. Sensitivity analysis showed that the MR results were robust [level pleiotropy, male: (MR-Egger, intercept = 0.1967434; se = 0.1186876; P = .2392406); female: (MR-Egger, intercept = -0.05902506; se = 0.05362049; P = .3211367)]. To further validate the impact of COVID-19 on infertility, we added a covariate (sex hormone binding global levels, abortion) to the MR analysis, which is a multivariate MR analysis. According to univariate and multivariate MR analyses, the evidence does not support that COVID-19 is a causal risk factor for infertility in European population. This information can provide information for doctors in reproductive centers when managing infertility patients.
| S-EPMC10919494 | biostudies-literature
Project description:We conducted Mendelian randomization analyses to investigate the associations of serum parathyroid hormone (S-PTH) and serum 25-hydroxyvitamin D (S-25OHD) concentrations with Alzheimer's disease (AD). Five and seven single nucleotide polymorphisms associated with S-PTH and S-25OHD concentrations, respectively, were used as instrumental variables. Data for AD were acquired from the International Genomics of Alzheimer's Project (17,008 AD cases and 37,154 controls). Genetically higher S-PTH concentrations were not associated with AD (odds ratio per standard deviation increase in S-PTH = 1.11; 95% CI 0.97?1.26; p = 0.12). In contrast, all seven 25OHD-increasing alleles were inversely associated with AD and two of the associations were statistically significant (p < 0.05). The odds ratio of AD per genetically-predicted one standard deviation increase in S-25OHD was 0.86 (95% CI 0.78?0.94; p = 0.002). This study provides evidence that vitamin D may play a role in AD but found no significant association between S-PTH and AD.
| S-EPMC6165184 | biostudies-literature