Causal association of serum vitamin D levels with urolithiasis: a bidirectional two-sample Mendelian randomization study.

In light of inconsistent evidence from previous observational studies regarding the correlation between serum vitamin D levels and urolithiasis, this study aimed to investigate the genome-wide causal association between genetically predicted serum 25(OH)D levels and urolithiasis using the Mendelian randomization (MR) approach. In this study, we utilized genome-wide association studies (GWAS) summary statistics from the UK Biobank and SUNLIGHT consortium for serum vitamin D levels, as well as urolithiasis data from FinnGen. We employed bidirectional two-sample MR analysis to evaluate potential causal relationships. The primary MR analysis relied on the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode approaches. Sensitivity analyses were conducted to ensure result robustness, including Cochran's Q test, MR-Egger intercept test, leave-one-out tests, and MR pleiotropy residual sum and outlier (MR-PRESSO) test. The MR analysis indicated no significant causal effects of serum 25(OH)D levels on urolithiasis [IVW method: (kidney and ureteral stones: OR = 1.134;95% CI, 0.953 to 1.350, p = 0.155; lower urinary tract stones: OR = 1.158; 95% CI, 0.806 to 1.666, p = 0.428)]. However, according to the IVW results, genetically predicted kidney and ureteral stones were associated with decreased serum 25(OH)D levels (beta = -0.025; 95% CI, -0.048 to -0.003; p = 0.028), while they did not indicate a causal effect of lower urinary tract stones on serum 25(OH)D levels (beta = -0.002; 95% CI, -0.013 to -0.008; p = 0.662). A sensitivity analysis suggested the robustness of these causal associations. Our MR study did not provide evidence supporting a causal association between serum 25(OH)D levels and urolithiasis among individuals of European descent. However, there might exist a negative causal association between kidney and ureteral stones and serum 25(OH)D levels.

Zhang QF ，Zhang HZ ，Wang S ，Zeng LY ... -  《-》

No causal association between serum vitamin D levels and bronchiectasis: A Mendelian randomization analysis.

Observational studies have reported an association between Vitamin D deficiency and an increased risk of bronchiectasis. This study aims to investigate the causal relationship between Vitamin D levels and bronchiectasis using a 2-sample Mendelian randomization (MR) analysis. Data from 2 genome-wide association studies (GWAS) based on European ancestry were analyzed: serum vitamin D levels (sample size = 441,291 [UK Biobank]) and bronchiectasis (sample size = 187,830 [cases = 1107, controls = 186,723; FinnGen]). Inverse-variance weighted (IVW) analysis was primarily used to assess the causal effect of 25(OH)D levels on bronchiectasis, supplemented by Mendelian randomization Egger regression (MR-Egger), weighted median, simple mode, and weighted mode analyses. Additionally, MR-Egger intercept test and MR-Pleiotropy Residual Sum and Outlier methods were implemented to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis and Bayesian weighted Mendelian randomization was also used to assess the robustness of the results. The MR analysis suggested no significant causal effects of serum 25(OH)D levels on bronchiectasis using the IVW method (odds ratio = 1.550; 95% confidence interval [CI]: 0.908-2.315; P = .120). These results were consistent across MR-Egger regression, weighted median, simple mode, and weighted mode analyses. No significant heterogeneity, pleiotropy, or bias was detected in instrumental variables. Additionally, no evidence supported the causal effects of bronchiectasis on serum vitamin D levels (β = -0.002, 95% CI: -0.007 to 0.003; P = .463). Our study found no significant causal association between serum 25(OH)D levels and bronchiectasis, in either direction. A larger sample-sized randomized controlled trial (RCT) is needed to further investigate this potential causal relationship.

Pan W ，Huang Z ，Deng H ，Huang H ，Yu K ... -  《-》

The association between serum 25-hydroxyvitamin D levels and erectile dysfunction: a two-sample Mendelian randomization analysis.

Considering that vascular endothelial cell dysfunction is the pathological basis of erectile dysfunction (ED), and recognizing the beneficial effects of 25-hydroxyvitamin D (25(OH)D) on vascular endothelial cell protection, the researchers diligently investigated the causal relationship between serum 25(OH)D levels and ED. However, inconsistent clinical evidence has left the association between serum 25(OH)D levels and ED unclear. The objective of this work was to employ Mendelian randomization (MR) analysis to ascertain the potential causal relationship between serum 25(OH)D levels and ED. We conducted a two-sample MR analysis utilizing data from publicly available genome-wide association studies (GWASs). The primary analysis method for the MR analysis was the inverse-variance weighted (IVW) method, supplemented by the MR-Egger and weighted median methods. In addition, we evaluated heterogeneity with Cochran's Q test, assessed pleiotropy using the MR-Egger intercept test, and performed a leave-one-out analysis to identify single-nucleotide polymorphisms (SNPs) with potential effects. Outliers were detected using MR-pleiotropy residual sum and outlier (MR-PRESSO). Genetically predicted serum 25(OH)D levels were not found to be causally associated with ED in IVW method (OR = 1.028, 95% CI = 0.845-1.250, P = 0.785), MR-Egger method (OR = 1.057, 95% CI = 0.782-1.430, P = 0.720), and weighted median method (OR = 1.225, 95% CI = 0.920-1.633, P = 0.165). The results of sensitivity analyses reinforced our conclusion, indicating no evidence of heterogeneity or directional pleiotropy. In summary, our findings do not substantiate a genetic-level causal link between serum 25(OH)D levels and the prevalence of ED. Nonetheless, future research, including larger MR studies, clinical trials, and additional observational studies, is essential to validate and reinforce the outcomes of our present study.

Gao D ，Chen C ，Wu Z ，Li H ，Xie C ，Tang B ... -  《-》

Association of walking pace and risk of stroke: A two- sample mendelian randomization study in a European ancestry cohort.

Liang C ，Huang X ，Pu Y ，Zhang P ，Wang R ... -  《-》

Non-Alcoholic Fatty Liver Disease and Vitamin D in the UK Biobank: A Two-Sample Bidirectional Mendelian Randomisation Study.

Zhang Z ，Burrows K ，Fuller H ，Speliotes EK ，Abeysekera KWM ，Thorne JL ，Lewis SJ ，Zulyniak MA ，Moore JB ... -  《Nutrients》