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.
Objective To investigate the potential causal associations between 731 immune cell traits and atherosclerosis by Mendelian randomization (MR) analysis. Methods Using single nucleotide polymorphisms (SNPs) as instrumental variables, genome-wide association study (GWAS) summary statistics (GCST90001391 to GCST90002121) for 731 immune cell traits were obtained from the GWAS Catalog database, and the atherosclerosis dataset (finn-b-I9_CORATHER) was retrieved from the IEU database for MR analysis. The inverse variance weighted method, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed to estimate the causal effects between the 731 immune cell traits and atherosclerosis, using odds ratio (OR) with 95% confidence interval (CI) as the effect size. Cochran Q test was used to assess heterogeneity. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method. Leave-one-out analysis was conducted to examine the sensitivity of the causal estimates to individual SNPs. Results MR analysis revealed potential causal associations between 24 immune cell traits and atherosclerosis (P<0.05). Among them, human leucocyte antigen (HLA)-DR on plasmacytoid dendritic cells (DC) [OR=1.035, 95%CI (1.016, 1.054), P<0.001] and hematopoietic stem cell absolute count (HSCAC) [OR=1.049, 95%CI (1.021, 1.077), P<0.001] showed significant positive causal associations with atherosclerosis (P≤0.001), whereas CD86 on CD62L+ myeloid DC [OR=0.953, 95%CI (0.926, 0.981), P=0.001] exhibited a significant negative causal association with atherosclerosis (P≤0.001). The results of Cochran Q test, MR-Egger regression, and MR-PRESSO indicated P-values>0.05, suggesting no evidence of heterogeneity or horizontal pleiotropy in the causal estimates for these three immune cell traits. Reverse MR analysis, using the 24 immune cell traits as outcome variables, showed no evidence of causal association (P>0.05), supporting a unidirectional causal relationship from immune cells to atherosclerosis. Conclusion HLA-DR on plasmacytoid DC and HSCAC may serve as risk factors for atherosclerosis, while CD86 on CD62L+ myeloid DC may play a protective role against atherosclerosis.
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 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 analyze the causal relationship between the intake of cheese or tea and the risk of gastroesophageal reflux disease (GERD). MethodsUsing a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or tea intake were used as instrumental variables. The causal effect of milk or tea intake on the risk of GERD was investigated using the MR Egger method, the weighted median method, the inverse-variance weighted (IVW) random-effects model, and the IVW fixed-effects model. Multivariable analysis was conducted using the MR Egger method, and leave-one-out sensitivity analysis was performed to validate the reliability of the data. ResultsCheese intake could reduce the occurrence of GERD [IVW random-effects model β=–1.010, 95%CI (0.265, 0.502), P<0.05], while tea intake could lead to the occurrence of GERD [IVW random-effects model β=0.288, 95%CI (1.062, 1.673), P<0.05]. ConclusionCheese intake may have a positive causal relationship with reducing the risk of GERD occurrence, while tea intake may have a positive causal relationship with increasing the risk of GERD occurrence.
Objective This study employs Mendelian randomization analysis to explore the causal relationship between dietary habits and systemic lupus erythematosus (SLE). MethodsWe obtained data from the MRC-IEU database on five dietary habits as instrumental variables for exposure "never eating dairy products" "never eating eggs or foods containing eggs" "never eating sugar or foods/drinks containing sugar" "never eating wheat products" and "I eat all of the above". Summary data related to SLE were retrieved from the MRC-IEU database for the discovery cohort (designated as MSLE) and from a Finnish database for the validation cohort (recorded as FSLE). Two-sample Mendelian randomization analyses were conducted using inverse variance weighting (IVW), MR-Egger, weighted median, Simple Mode, and Weighted Mode methods to investigate the causal relationship between dietary habits and SLE. The MR-Egger intercept test was performed to assess the presence of horizontal pleiotropy, while the leave-one-out method was employed to verify the stability of the results, with Cochran’s Q test and funnel plots used to evaluate heterogeneity. ResultsMendelian randomization analysis indicated that never eating wheat products increases the risk of developing SLE (IVW: P<0.05). In contrast, there was no significant causal relationship between the consumption of dairy products, eggs or foods containing eggs, or the consumption of all of the above with SLE (IVW: P>0.05). Additionally, there was no significant causal relationship between never sugar or foods/drinks containing sugar and MSLE (IVW: P=0.877), although a potential causal association with FSLE was suggested (IVW: P=0.016). The MR-Egger intercept test indicated no evidence of horizontal pleiotropy (P>0.05). ConclusionNever eating wheat products may be an independent risk factor for SLE. However, the causal relationship between never sugar or foods/drinks containing sugar and SLE remains indeterminate.
Objective To investigate the causal relationships between various circulating micronutrients and aneurysms at different sites using Mendelian randomization (MR) analysis. Methods Summary-level genetic data for 15 common blood micronutrients, including vitamin D, calcium, iron, copper, selenium, zinc, folate, carotene, vitamin C, vitamin B12, vitamin E, magnesium, vitamin B6, omega-3 fatty acids, and homocysteine, were obtained from the IEU Open GWAS database. Genetic associations with aneurysms, including intracranial aneurysm and thoracic aortic aneurysm, were retrieved from the GWAS Catalog and the FinnGen consortium. Bidirectional MR analyses were performed using seven MR approaches, with the inverse-variance weighted (IVW) method as the primary analysis. Multiple sensitivity analyses and visualization tools were used to assess pleiotropy and heterogeneity. Furthermore, multivariable MR was applied to explore the interactions and independent effects of multiple micronutrients on aneurysm risk, and meta-analysis was employed to integrate results from different data sources and minimize bias. Results Through multiple MR and sensitivity analyses, combined with multivariate MR and meta-analysis, the results confirmed that elevated blood levels of vitamin D could significantly increase the risk of intracranial aneurysm [odds ratio (OR)=1.65, 95% confidence interval (CI) (1.20, 2.29), P=0.002], while omega-3 fatty acids [OR=0.82, 95%CI (0.73, 0.92), P=0.001] could significantly reduce the risk. For thoracic aortic aneurysm, selenium [OR=1.08, 95%CI (1.00, 1.15), P=0.042] and folate [OR=1.45, 95%CI (1.13, 1.87), P=0.004] were identified as potential risk factors. No heterogeneity or horizontal pleiotropy was detected, and no reverse causality was found between micronutrients and aneurysm development. Conclusions Variations in circulating micronutrient levels can influence the risk of aneurysm development. These findings provide new insights into the potential roles of micronutrients in aneurysm prevention and treatment and offer a scientific basis for developing targeted clinical intervention strategies.
ObjectiveTo conduct a Mendelian randomization (MR) analysis to elucidate the potential causal relationship between sarcopenia (SA) and knee osteoarthritis (KOA). MethodsThree SA-related traits were selected as exposure factors from the summary data of the genome-wide association studies database (IEU GWAS). KOA and hospital-diagnosed osteoarthritis of the knee (osteoarthritis of the knee hospital diagnosed) were chosen as outcome factors. The inverse variance-weighted (IVW) method was employed as the primary analytical approach to evaluate the causal relationship between SA and KOA. Heterogeneity tests, sensitivity analyses, and pleiotropy analyses were conducted to validate the reliability of the results. ResultsThe MR results indicated a substantial causal relationship between genetically predicted appendicular muscle mass (OR=1.079, 95%CI 1.015 to 1.147, P=0.015 5), walking speed (OR=0.157, 95%CI 0.101 to 0.248, P<0.001). No significant causal relationship was found between grip strength and KOA (OR=1.318, 95%CI 0.933 to 1.859, P=0.116 6), and the sensitivity analysis results did not exhibit horizontal pleiotropy. ConclusionSA may have a causal relationship with KOA, and appendicular muscle mass and walking speed may be risk factors for the occurrence and development of KOA.
ObjectiveThis study applied Mendelian randomization to explore the potential causal relationship between inflammatory factors and diabetic nephropathy. MethodsSummary-level data from genome-wide association studies of inflammatory factors and diabetic nephropathy were used, and inverse variance weighted analysis was used as the primary analytical method, complemented by results from weighted median, MR-Egger regression, simple model, and median model approaches. Sensitivity analysis was used to test the reliability of the MR analysis results. ResultsIn the inverse variance weighted method, stem cell factor (OR=1.28, 95%CI 1.04 to 1.58, P=0.020) and interferon-γ (OR=1.36, 95%CI 1.10 to 1.70, P=0.005) were positively correlated with diabetic nephropathy, and diabetic nephropathy was positively correlated with interferon-inducible protein 10 (OR=0.90, 95%CI 0.83 to 0.98, P=0.012) were negatively correlated with diabetic nephropathy. Sensitivity analysis showed that MR analysis was reliable. ConclusionStem cell factors and interferon-γ are associated with an increased risk of developing diabetic nephropathy, and diabetic nephropathy decreases the expression of interferon-inducible protein 10 in vivo. Our results demonstrate a potential causal relationship between inflammatory factors and the development of diabetic nephropathy. This finding is of clinical significance for the pre-diagnosis and treatment of diabetic nephropathy.