Objective To analyze the causal relationship between gut microbiota and tic disorder based on Mendelian randomization (MR). Methods A total of 196 known microbiota (9 phyla, 16 classes, 20 orders, 32 families, and 119 genera) in the human intestinal microbiota dataset downloaded from the MiBioGen database were selected as the exposure factors, and the dataset of tic disorder (finn-b-KRA_PSY_TIC) containing 172 patients and 218620 controls was downloaded from the genome-wide association study database as the outcome variable. Inverse variance weighted was used as the main analysis method, and the causal relationship between gut microbiota and tic disorder was evaluated using odds ratio (OR) and its 95% confidence interval (CI). Horizontal pleiotropy was tested by MR-Egger intercept and MR-PRESSO global test, heterogeneity was assessed by Cochran’s Q test, and sensitivity analysis was performed by leave-one-out method. Results Inverse variance weighted results showed that the Family Rhodospirillaceae [OR=0.398, 95%CI (0.191, 0.831), P=0.014], Order Rhodospirillales [OR=0.349, 95%CI (0.164, 0.743), P=0.006], and Parasutterella [OR=0.392, 95%CI (0.171, 0.898), P=0.027] had negative causal relationships with tic disorder. The Genus Lachnospira [OR=8.784, 95%CI (1.160, 66.496), P=0.035] and Candidatus Soleaferrea [OR=2.572, 95%CI (1.161, 5.695), P=0.020] had positive causal relationships with tic disorder. In addition, MR-Egger intercept and MR-PRESSO global test showed no horizontal pleiotropy, Cochran’s Q test showed no heterogeneity, and leave-one-out sensitivity analysis showed the results were stable. Conclusions A causal relationship exists between gut microbiota and tic disorder. The Family Rhodospirillaceae, Order Rhodospirillales, and Parasutterella are associated with a decreased risk of tic disorder, while the Genus Lachnospira and Candidatus Soleaverea can increase the risk of tic disorder.
ObjectiveThyroid nodules are an exceptionally common thyroid disorder. Past studies suggested a possible link between thyroid diseases and breast neoplasms. However, few studies have delved into the causal relationship between thyroid nodules and breast neoplasms. This study conducted a Mendelian randomization (MR) analysis to further investigate the causal relationship between them. MethodsThis study was conducted using data sourced from genome-wide association study (GWAS) summary datasets. The study focused on thyroid nodules, benign breast tumors, and malignant breast cancers as the research objects, and relevant single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). The inverse-variance weighted (IVW) was primarily used to assess the causal relationship between thyroid nodules and breast neoplasms. Cochran’s Q test was employed to detect heterogeneity, while MR-Egger intercept and MR-PRESSO were used to test for pleiotropy. Sensitivity analysis was conducted using the leave-one-out method. ResultsThere was a significant causal relationship between thyroid nodules and malignant neoplasm of breast (OR=0.88, 95%CI 0.83 to 0.95, P<0.01), with no evidence of reverse causality between them (OR=1.01, 95%CI 0.99 to 1.03, P=0.16). No causal relationship was found between thyroid nodules and benign neoplasm of breast, as indicated by both forward MR analysis (OR=0.97, 95%CI 0.89 to 1.06, P=0.51) and reverse MR analysis (OR=0.97, 95%CI 0.92 to 1.04, P=0.40). Sensitivity analyses suggested that the study findings were accurate and reliable. ConclusionThe present study identifies thyroid nodules as a potential protective factor for malignant neoplasm of breast.
Objective To explore the causal relationship between breast cancer and rotator cuff injury using bidirectional two-sample Mendelian randomization. Methods Instrumental variables for breast cancer and rotator cuff injury were extracted from published genome-wide association study data. The positive study used breast cancer as the exposure and rotator cuff injury as the outcome, with single nucleotide polymorphisms (SNPs) closely associated with both breast cancer and rotator cuff injury as genetic instrumental variables. The reverse study used rotator cuff injury as the exposure and breast cancer as the outcome, with SNPs closely associated with both breast cancer and rotator cuff injury as genetic instrumental variables. Bidirectional MR analysis was conducted using five models: inverse variance weighted (IVW), simple model, weighted median, weighted model, and MR-Egger to assess the causal relationship between breast cancer and rotator cuff injury. Cochran Q test was used to detect heterogeneity, MR-Egger to detect horizontal pleiotropy, and leave-one-out method for sensitivity analysis to ensure the robustness of the results. Results A total of 51 SNPs closely associated with breast cancer were included in the forward study. The results indicated a positive causal association between breast cancer and an increased risk of rotator cuff injury [IVW: odds ratio=1.08, 95% confidence interval (1.02, 1.12), P=0.014], with no evidence of heterogeneity in the causal relationship between breast cancer and rotator cuff injury (P>0.05). Horizontal pleiotropy test results showed no horizontal pleiotropy in the SNPs (P>0.05). Leave-one-out test results did not detect any SNP with a large impact on the results. In the reverse study, a total of 3 SNPs related to rotator cuff injury were included as instrumental variables. There was no strong evidence that rotator cuff injury had a causal effect on breast cancer incidence [IVW: odds ratio=0.95, 95% confidence interval (0.86, 1.05), P=0.334]. Conclusions There is a potential causal association between breast cancer and rotator cuff injury. Therefore, it is suggested to increase the screening for rotator cuff injury in breast cancer patients.
ObjectiveTo explore the potential causal relationship between 91 inflammatory factors and the risk of lung cancer (LC). MethodsBy extracting related data of inflammatory factors and LC and its subtypes from public databases of genome-wide association studies (GWAS), bidirectional, repeated, multivariable Mendelian randomization (MR) and subgroup MR methods were used for analysis. The inverse variance weighted method was mainly used for causal inference, and a series of sensitivity analyses were applied to verify the strength of the results. ResultsHigher levels of CD5, interleukin-18 (IL-18), and oncostatin-M (OSM) were causally associated with a lower risk of LC, while nerve growth factor-β (NGF-β) and S100 calcium-binding protein A12 (S100A12) were associated with an increased risk of LC. Subgroup MR analysis results showed that IL-18 had a causal relationship with a reduced risk of lung adenocarcinoma, while NGF-β and S100A12 had a causal relationship with an increased risk of lung adenocarcinoma; CD5 and OSM had a causal relationship with a reduced risk of lung squamous cell carcinoma; NGF-β had a causal relationship with an increased risk of small cell lung cancer. ConclusionFive inflammatory factors, including CD5, IL-18, OSM, NGF-β, and S100A12 have a causal correlation with the risk of LC, providing potential targets for early screening of LC patients and development of therapeutic drugs.
Objective To explore the relationship between the gut microbiome (GM) and psoriasis using a two-sample two-way Mendelian randomization (MR) approach. Methods The forward analysis uses the gut microbiota as the exposure factor, and its genetic data are derived from the genome-wide association study dataset published by the MiBioGen consortium. Psoriasis was used as the outcome variable, and its genetic data were obtained from the UK Biobank. The reverse MR analysis, on the other hand, took psoriasis as the exposure and the specific gut microbiota taxonomic units identified in the forward analysis as the outcome variable. MR analysis was conducted using maximum likelihood, MR Egger regression, weighted median, inverse variance weighting (IVW), and weighted models to study the causal relationship between the gut microbiota and psoriasis. Then, sensitivity analyses including horizontal pleiotropy test, Cochran’s Q test, and leave-one-out analysis were used to evaluate the reliability of the results. Results A total of 51 single nucleotide polymorphisms from 5 fungi were included in the forward study. The forward IVW analysis results showed that, the class Mollicutes [odds ratio (OR)=1.003, 95% confidence interval (CI) (1.001, 1.006), P=0.004], genus Lachnospiraceae FCS020 group [OR=1.003, 95%CI (1.000, 1.006), P=0.041], and phylum Tenericutes [OR=1.003, 95%CI (1.001, 1.006), P=0.004] were causally associated with an increased risk of psoriasis. The family Victivallaceae [OR=0.998, 95%CI (0.997, 1.000), P=0.005] and order Pasteurellales [OR=0.998, 95%CI (0.996, 1.000), P=0.047] were also linked to a decreased risk of psoriasis. The results of the sensitivity analysis were robust. There was no evidence of a reverse causal relationship from psoriasis to the identified bacterial taxa found in the results of reverse MR analysis results. Conclusions The abundance of three species, class Mollicutes, genus Lachnospiraceae and phylum Tenericutes, may increase the risk of psoriasis. The abundance of two species, family Victivallaceae and order Pasteurellales may reduce the risk of psoriasis. These results provide new directions for the prevention and treatment of psoriasis in the future, but further research is needed to explore how the aforementioned microbiome affects the progression of psoriasis.
ObjectiveTo assess the causal relationship between cervical vertebra related disorders and essential hypertension using a bidirectional two-sample Mendelian randomization study approach. MethodsThe research data comes from the genome-wide association study dataset. Four types of cervical vertebra related disorders: cervicalgia, cervical disc disorders, cervical root disorders, injury of nerves and spinal cord at neck level, as well as data on essential hypertension, were selected for the study. Relevant single nucleotide polymorphisms were selected as instrumental variables to assess the causal relationship between cervical vertebra related disorders and essential hypertension mainly by inverse variance weighted model ratio. Cochran's Q test was used to detect heterogeneity, MR-Egger intercept term and MR-PRESSO was used to detect multiplicity, and leave-one-out method was used for sensitivity analysis. ResultsCervicalgia had a positive causal relationship with the essential hypertension (OR=1.01, 95%CI 1.00 to1.02, P=0.019). Essential hypertension had a positive causal relationship with the cervical disc disorders (OR=4.08, 95%CI 1.57 to10.61, P=0.004). There was no significant causal relationship between cervical root disorders, injury of nerves and spinal cord at neck level and essential hypertension. Reliability assessment indicates that the study results were reliable. ConclusionCervicalgia is a risk factor for essential hypertension; Essential hypertension is a risk factor for cervical disc lesions; There is no correlation between cervical root disorders, injury of nerves and spinal cord at neck level and essential hypertension.
ObjectiveTo investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). MethodsGenome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and Finngen databases, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. ResultsIVW analysis results showed that Actinomycetes [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222,0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. ConclusionActinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.
ObjectiveTo explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. MethodsWe employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. ResultsOur research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ may play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. ConclusionPD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.
Objective To explore the causal association between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Methods Using the summary statistical data from the FinnGen biological sample library and IEU OpenGWAS database, the relationship between OSA and VTE, including deep vein thrombosis (DVT) and pulmonary embolism, was explored through Mendelian randomization (MR) method, with inverse variance weighted (IVW) as the main analysis method. Results The results of univariate MR analysis using IVW method showed that OSA was associated with VTE and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.204 (1.067, 1.351) and 1.352 (1.179, 1.544), respectively. There was no correlation with DVT (P>0.05). Multivariate MR analysis showed that after adjustment for confounding factors (smoking, diabetes, obesity and cancer), OSA was associated with VTE, DVT and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.168 (1.053, 1.322), 1.247 (1.064, 1.491) and 1.158 (1.021, 1.326), respectively. Conclusion OSA increases the risk of VTE, DVT, and pulmonary embolism.
Objective To introduce the use of Central Randomization System in clinical trials. Methods We discussed the application of Central Randomization System in clinical trials from object management, drug management and user management, and made a brief description of minimization method. Results Central Randomization Systems can guarantee the nnplementation of the scheme of randomization, and can be used in clinical trials with minimization. Conclusion Central Randomization Systems are feasible in clinical trials especially in traditional Chinese medicine and open clinical trials.