The causal relationship between 25-hydroxyvitamin D and serum lipids levels: A bidirectional two-sample mendelian randomization study
Ontology highlight
ABSTRACT:
SUBMITTER: Yin T
PROVIDER: S-EPMC10866529 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Observational studies have confirmed that 25-hydroxyvitamin D (25(OH)D) is associated with pulmonary hypertension (PH), but the causal association between each other is unclear. Therefore, Mendelian randomization (MR) method was performed to validate the causal association between PH and serum 25(OH)D levels. The summary data for 25(OH)D and PH were from the National Human Genome Research Institute-European Bioinformatics Institute. Catalog of human genome-wide association studies and FinnGen biobank consortium. MR analysis was utilized to explore the potential causal association between PH and 25(OH)D. To evaluate this association, inverse variance weighting was considered as the primary method. Cochran's Q test, MR-Egger intercept test, and "leave-one-out" sensitivity analyses were utilized to control the pleiotropy and heterogeneity in the study. Two-sample MR analysis revealed an inverse causal relationship between 25(OH)D and PH (odds ratio: 0.376, 95% confidence interval: 0.162-0.876, p = 2.334 × 10-2). There was no significant heterogeneity and pleiotropy. The present study confirmed the inverse causal relationship between 25(OH)D and PH. This pathway may provide another treatment pathway in PH. Further studies to elucidate this pathway is indicated.
| S-EPMC10918714 | biostudies-literature
Project description:BackgroundSerum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain.ObjectiveConduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk.MethodGenome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method.ResultThere were 103 SNPs utilized as instrumental variables (p < 5 × 10-8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models.ConclusionThe present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.
| S-EPMC11200040 | 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:ObjectiveObservational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy.MethodsWe conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25 (OH) D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity.ResultsMR analyzed the relationship between 25 (OH) D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25 (OH) D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval [CI]: 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy.SignificanceHigher serum levels of 25 (OH) D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.
| S-EPMC10472413 | biostudies-literature
Project description:BackgroundAccumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD.MethodsA bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well.ResultsUvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn't support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280).ConclusionOur findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary.
| S-EPMC10034407 | biostudies-literature
Project description:Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear. Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83-0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96-1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust. Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.
| S-EPMC9534573 | biostudies-literature
Project description:Background: Although observational studies have demonstrated that blood lipids were associated with systemic lupus erythematosus (SLE), the causality of this association remains elusive as traditional observational studies were prone to confounding and reverse causality biases. Here, this study attempted to reveal the potential causal link between SLE and the levels of four blood lipids (HDL cholesterol, LDL cholesterol, TG, and TC). Methods: Bidirectional two-sample Mendelian randomization (MR) was employed to explore the unconfounded causal associations between the four blood lipids and SLE. In addition, regression-based Multivariate MR (MVMR) to quantify the possible mediation effects of blood lipids on SLE. After a rigorous evaluation of the quality of studies, the single-nucleotide polymorphisms (SNPs) associated with the four blood lipids were selected from the Global Lipids Genetic Consortium (GLGC) consisted of 188,577 individuals of European ancestry, and the SNPs related to SLE were selected from a large-scale genome-wide association study (GWAS) database named IEU GWAS. Subsequently, MR analyses were conducted with inverse-variance weighted (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression. Sensitivity analyses were performed to verify whether heterogeneity and pleiotropy led to bias in the MR results. Results: Bidirectional two-sample MR results demonstrated that there was no significant causal association between SLE and the four blood lipids (When setting SLE as outcome, HDL cholesterol and SLE, IVW OR: 1.32, 95% CI: 1.05∼1.66, p = 1.78E-02; LDL cholesterol and SLE, IVW OR: 1.26, 95% CI: 1.04∼1.53, p = 2.04E-02; TG and SLE, IVW OR: 1.04, 95% CI: 0.71∼1.51, p = 8.44E-01; TC and SLE, IVW OR: 1.07, 95% CI: 0.89∼1.29, p = 4.42E-01; When setting SLE as exposure, SLE and HDL cholesterol, IVW OR: 1.00, 95% CI: 0.99∼1.01, p = 9.51E-01; SLE and LDL cholesterol, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 3.14E-01; SLE and TG, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.30E-02; SLE and TC, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.56E-01). Our MVMR analysis also provided little evidence that genetically determined lipid traits were significantly associated with the risk of SLE (HDL cholesterol and SLE, p = 9.63E-02; LDL cholesterol and SLE, p = 9.63E-02; TG and SLE, p = 8.44E-01; TC and SLE, p = 4.42E-01). Conclusion: In conclusion, these data provide evidence that genetic changes in lipid traits are not significantly associated with SLE risk in the European population.
| S-EPMC9043646 | 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:BackgroundUric acid is the final metabolic product of purines in the human body and has been implicated in the pathogenesis of various diseases. Nevertheless, the relationship between serum uric acid levels and male infertility remains inconclusive. This Mendelian randomization (MR) study aims to elucidate the potential impact of serum uric acid levels on the risk of male infertility.MethodsWe conducted the bidirectional MR analysis utilizing summary data from genome-wide association studies (GWAS) on serum uric acid levels and male infertility. The inverse variance weighted (IVW) method was employed to evaluate the primary outcomes, and multivariate MR analyses were conducted to combine estimates of the causal effects of multiple risk factors. Additionally, sensitivity analyses were performed to confirm the robustness of the results.ResultsIn the univariable MR analysis, serum uric acid levels did not exhibit a significant association with the risk of male infertility [IVW odds ratio (OR) 0.92, 95% confidence interval (CI): 0.614-1.390, P=0.70]. Similar conclusions were drawn from the reverse MR analysis (IVW OR 1.000, 95% CI: 0.997-1.003, P=0.96). In the multivariable MR (MVMR) analysis, after adjusting for confounding factors such as body mass index (BMI), type 2 diabetes, alcohol consumption, and smoking, serum uric acid levels remained unassociated with male infertility (IVW OR 0.839, 95% CI: 0.613-1.148, P=0.27). Consistent results were observed in the reverse analysis (IVW OR 1.003, 95% CI: 0.994-1.012, P=0.49).ConclusionsOur study provides genetic evidence indicating no significant causal relationship between serum uric acid levels and male infertility in the general population, suggesting that serum uric acid is not a potential risk factor for male infertility.
| S-EPMC11650356 | biostudies-literature
Project description:BackgroundThe relationship between serum lipids and cholecystitis is still under investigation. To examine the causal effect of serum lipids on cholecystitis using the Mendelian randomization method.MethodsWe conducted univariable Mendelian randomization (MR) analyses using summary statistics from two independent genome-wide association studies (GWAS) on serum lipids (n = 132,908) and cholecystitis (n = 361,194). Mainly, the inverse-variance weighted (IVW) method was utilized to combine each SNP's causal estimation, and the MR-Egger was adopted as a complementary method, together with the weighted median. Cochrane's Q value was employed to appraise heterogeneity. The MR-Egger intercept and MR-PRESSO were used to detect the horizontal pleiotropy.ResultsOur univariable results displayed a minor protective effect of serum low-density lipoprotein (LDL) cholesterol (OR [95% CI] = 0.9984483 [0.9984499, 0.9984468]; p = 0.008) on cholecystitis. No significant causal effect of total cholesterol (TC) (OR [95% CI] = 0.9994228 [0.9994222, 0.9994233]; p = 0.296), triglycerides (OR [95% CI] = 0.9990893 [0.9990882, 0.9990903]; p = 0.238) and high-density lipoprotein (HDL) cholesterol (OR [95% CI] = 0.9997020 [0.9997017, 0.9997023]; p = 0.565) was found on cholecystitis.ConclusionThese findings suggest that LDL cholesterolhas a slight protective effect on cholecystitis, which can be easily affected by confounding factors. TC, triglycerides and HDL cholesterol don't have causal effect on cholecystitis. The protective effect of serum lipids on cholecystitis, though possible, remain less certain.
| S-EPMC8447629 | biostudies-literature