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 ... -  《-》

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 ... -  《-》

HIV and risk of hypertension: a two-sample Mendelian randomization study.

Previous studies have shown that human immunodeficiency virus (HIV) infection is associated with hypertension; however, the results of these studies are affected by a variety of confounding factors. There is no definite evidence to prove a causal relationship between these two factors. This study aimed to investigate the causal relationship between HIV infection and hypertension. A two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) statistics published online. The data were collected mainly from the OpenGWAS and FinnGen databases. The HIV database contained 357 HIV patients and 218,435 control patients; the hypertension database contained 54,358 patients and 408,652 control patients; and the blood pressure database contained 436,424 samples. Random effect inverse variance weighting (IVW) was used as the main analysis method, weighted median and Mr-Egger analysis methods were used to ensure the accuracy of the results, and Cochran's Q test and Mr-Egger regression methods were used to detect heterogeneity and correct multiple horizontal effects. Finally, the leave-one-out method was used to analyse the reliability of the test results. In order to further verify the research results, different databases were used and the same statistical method was used for a replication analysis. In order to prevent false positive results caused by multiple tests, Bonferroni correction is used to correct the statistical results. After screening, a total of 9 SNPs (single-nucleotide polymorphisms) were selected as the instrumental variable (IV) used in this study. The IVW MR analysis results showed a causal relationship between HIV infection and the risk of hypertension (IVW: OR = 1.001, P = 0.03). When systolic blood pressure was the outcome, the IVW method results were positive (OR = 1.004, P = 0.01280), and when diastolic blood pressure was the outcome, the weighted median method results were positive (OR = 1.004, P = 0.04570). According to the sensitivity analysis, the results of this study were unlikely to be affected by heterogeneity and horizontal pleiotropy. The leave-one-out analysis showed that the results of this study did not change significantly with the elimination of a single SNP. In replication analysis, when diastolic blood pressure was taken as the outcome, the weighted median method was positive (OR = 1.042, P = 0.037). Sensitivity analysis shows that there is heterogeneity, but there is no horizontal pleiotropy. The leave-one-out analysis showed that the results of this study did not change significantly with the elimination of a single SNP. As the first exploratory study using MR method to study the causal relationship between HIV infection and hypertension and blood pressure, this study found that HIV infection may increase systolic and diastolic blood pressure and increase the risk of hypertension. PLWH, as a high-risk group of cardiovascular and cerebrovascular diseases, should prevent the occurrence of hypertension in order to further improve their quality of life. However, this study also has some limitations. The results of the relationship between HIV infection and hypertension and blood pressure may be affected by the lack of statistical efficacy. In order to further confirm this conclusion, more large-scale RCT or genetic studies should be carried out.

Zhu RW ，Guo HY ，Niu LN ，Deng M ，Li XF ，Jing L ... -  《BMC INFECTIOUS DISEASES》

The Association between Rheumatic Diseases and the Risk of Polycystic Ovary Syndrome: A Two-Sample Mendelian Randomization Analysis.

Wang J ，Zhou Q 《BRITISH JOURNAL OF HOSPITAL MEDICINE》

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 ... -  《-》