UNASSIGNED: Studies on the relationships between diseases of the urinary system and human plasma proteomes have identified several potential biomarkers. However, none of these studies have elucidated the causal relationships between plasma proteins and urolithiasis.
UNASSIGNED: The objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.
UNASSIGNED: A total of 1,400 metabolites were identified in the most comprehensive genome-wide association study (GWAS) of plasma metabolomics in a European population to date, and single-nucleotide polymorphisms (SNPs) were used as the instrumental variables for the plasma metabolites. The European GWAS data for urinary calculi included 482,123 case samples and 6,223 control samples (ebi-a-GCST90018935). The associations between the plasma metabolites and risk of urolithiasis were evaluated by inverse variance weighting (IVW) and supplemented by sensitivity analyses of the MR-Egger and MR-PRESSO tests.
UNASSIGNED: For the first time, we found a causal relationship between two plasma metabolites (p < 1.03 × 10-4) and urolithiasis (p < 0.05). The chemical 4-hydroxychlorothalonil, which is an intermediate product of the pesticide hydroxychlorothalonil, could promote urolithiasis (odds ratio (OR) = 1.12) as a risk factor. Moreover, 1-stearoyl-2-arachidonoyl-GPC, which is an important component of phospholipid metabolism in the human body, can inhibit urolithiasis (OR = 0.94).
UNASSIGNED: Our results suggest that blood metabolites can be used as blood markers and drug targets in the prevention, diagnosis, and treatment of urolithiasis; furthermore, our results can provide a basis for policy makers to formulate prevention and treatment policies for urolithiasis.

UNASSIGNED: Clinical observations indicate a correlation between the gut microbiota and overactive bladder (OAB) symptoms. Nevertheless, the causal relationship and mechanisms between gut microbiota and OAB symptoms remain elusive.
UNASSIGNED: Two-sample Mendelian randomization (MR) analyses were performed to assess the association between gut microbiota and OAB symptoms, including urinary incontinence (UI). Data were obtained from the MiBioGen International Consortium genome-wide association studies (GWAS) dataset and the IEU GWAS database. The inverse variance weighted method was used as the primary approach in the MR analysis, with the weighted median, MR-Egger, and weighted mode methods as supplementary approaches. Sensitivity analyses were employed to assess potential violations of the MR assumptions.
UNASSIGNED: Our analysis identified seven gut bacterial taxa with a causal relationship to OAB and nine gut bacterial taxa associated with UI. Genera Eubacteriumfissicatenumgroup, LachnospiraceaeNK4A136group, and Romboutsia were identified as protective factors against OAB, while genera Barnesiella, FamilyXIIIAD3011group, Odoribacter, and RuminococcaceaeUCG005 were associated with an increased risk of OAB. A higher abundance of the genus Coprococcus3, order Burkholderiales, and phylum Verrucomicrobia predicted a lower risk of UI. Conversely, the class Mollicutes, genus Ruminococcus gauvreauii group, order Mollicutes RF9, and phylum Firmicutes and Tenericutes were positively correlated with UI risk. The sensitivity analysis excluded the influence of potential heterogeneity and horizontal pleiotropy.
UNASSIGNED: This study revealed a causal relationship between gut microbiota and OAB symptoms, providing new insights and a theoretical foundation to identify biomarkers and therapeutic targets for patients with OAB symptoms.

UNASSIGNED: The relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis.
UNASSIGNED: The inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN.
UNASSIGNED: The IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08-1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05-1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC-IgAN and 14 MFI-IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates.
UNASSIGNED: Genetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN.

UNASSIGNED: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk.
UNASSIGNED: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran\'s Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity.
UNASSIGNED: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW = 0.94, 95% CI 0.93-0.96, P < 0.001). While neither MVPA (ORIVW = 0.99, 95% CI 0.67-1.47, P = 0.962) nor VPA (ORIVW = 0.80, 95% CI 0.29-2.18, P = 0.656) shows causal relationship on risk of SC.
UNASSIGNED: Our research suggests that PA is associated with a decrease in SC, provides a new perspective for future SC prevention. Our research findings bolster the hypothesis that increased levels of PA, characterized by average acceleration, are associated with a reduced risk of developing skin cancer. This has filled the gap of research on the causal relationship between PA and SC, and could pave the way for novel preventive strategies against skin cancer.

BACKGROUND: The relationship between serum lipids and sarcopenia remains unclear due to conflicting results in previous studies.
OBJECTIVE: To explore the associations and potential causality between serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and sarcopenia.
METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were analysed using multivariable regression and restricted cubic splines (RCSs) to assess the associations between serum lipids and sarcopenia. Bidirectional Mendelian randomization (MR) was employed to investigate the causal relationships with sarcopenia-related traits such as appendicular lean mass (ALM), hand grip strength, and usual walking pace.
RESULTS: Serum HDL-C and TG levels were inversely associated with ALMBMI, with each 1-unit increase linked to a 0.13 % and 1.32 % decrease, respectively. Elevated TG, but not HDL-C, LDL-C, or TC levels, was significantly associated with an increased risk of sarcopenia (P for trend = 0.001). RCS analysis revealed a log-shaped dose-response relationship between TG and sarcopenia risk (P overall <0.001, P non-linear <0.001), with a cutoff value of 92.75 mg/dL. Genetically predicted HDL-C, LDL-C, and TG were associated with ALM. Conversely, ALM showed an inverse causal relationship with all four serum lipids. Additionally, genetically predicted usual walking pace influenced HDL-C and TG levels (P < 0.001).
CONCLUSIONS: The study reveals a nonlinear association between TG levels and sarcopenia risk, and a bidirectional association between lipid profiles and muscle mass, underscoring the need for further research to elucidate these mechanisms.

BACKGROUND: Existing epidemiological studies have indicated a correlation between air pollutants and the occurrence of mental disorders. However, it is difficult to estimate the causal relationship between the two because of the limitations of traditional epidemiological research. In our study, we aimed to extensively explore the causal relationship between five types of air pollutants and four types of mental disorders.
METHODS: Based on the IEU OPEN GWAS database, we performed a two-sample MR analysis. The primary analysis method utilized was the inverse variance weighted (IVW) method, supplemented by the MR-Egger method and the weighted median method. Additionally, we conducted sensitivity analyses with the Cochran\'s Q statistic method, the leave-one-out method, and the MR-Egger intercept. We chose at least 4 GWAS datasets for each of the four psychiatric diseases and conducted a meta-analysis of our results of the MR analysis.
RESULTS: The meta-analysis\'s findings demonstrated a causal link between depression and PM2.5 (OR=1.020, 95 %CI: (1.010,1.030), P=0.001). PM10 and schizophrenia are also causally related (OR=1.136, 95 %CI: (1.034,1.248), P=0.008). Nitrogen oxides and bipolar disorder have a causal relationship (OR=1.002, 95 %CI: (1.000,1.003), P=0.022). Nitrogen oxides and schizophrenia have a high causal association (OR=1.439, 95 %CI: (1.183,1.752), P<0.001).
CONCLUSIONS: This study observed a causal association between increased concentrations of PM2.5, PM10, and nitrogen oxides and the occurrence of depression, schizophrenia, and bipolar disorder. Our research findings have certain guiding implications for treating and preventing mental disorders.

UNASSIGNED: Although descriptive studies have found an association between thyroid dysfunction (TD) and alopecia areata (AA), however, the causal relationship between TD and AA remains unclear. The purpose of this study is to investigate the causal relationship between the two and the specific directions.
UNASSIGNED: We performed large-scale, two-sample Mendelian randomization (MR) analyses to examine whether there was an association between TD (such as Graves\' disease (GD), Hashimoto\'s thyroiditis (HT), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), etc.) and AA. Genome-wide association study (GWAS) summary statistics for TD and AA were from the IEU OpenGwas project. The inverse variance-weighted (IVW) method was used as the primary analysis method to evaluate the causality between TD and AA, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. In addition, sensitivity analyses were performed to assess the reliability of the study results.
UNASSIGNED: Our study found that single nucleotide polymorphisms (SNPs) in HT (IVW OR = 1.396, 95% CI 1.030-1.892, P=0.031) and hypothyroidism (IVW OR = 1.431, 95% CI 1.138-1.799, P=0.002) significantly increased the risk of AA. Reverse MR analysis indicated that genetic susceptibility to AA (β=-0.029, 95%CI=-0.051 to -0.007, P=0.009) may be a risk for TRH. Positive MR analysis observed no statistically significant causal relationship between other TD and AA (IVW P>0.05). Reverse MR analysis also showed no statistically significant association between AA and other TD (IVW P>0.05) other than TRH. Furthermore, additional sensitivity analyses were performed, including a leave-one-out test, a heterogeneity test, and a pleiotropy test to assess the robustness of the results.
UNASSIGNED: This study provides a very comprehensive analysis of the causal relationship between TD and AA, providing convincing genetic evidence to support the causal relationship between TD and alopecia areata. It reveals some causes of AA patients, which is of great significance for the management and treatment of AA patients.

BACKGROUND: Evidence from various cohort studies indicate a potential association between depressive disorder and benign prostatic hyperplasia (BPH), yet findings are inconsistent. This study employs bidirectional two-sample Mendelian randomisation (MR) analysis to explore the causal relationship between BPH and major depressive disorder (MDD).
METHODS: Genetic variants strongly associated with MDD were extracted as instrumental variables conducted by the Psychiatric Genomics Consortium (PGC). Two sets of genetic variants associated with BPH were extracted from the recent FinnGen and Medical Research Council-Integrative Epidemiology Unit Consortium of BPH as the discovery and replication stages, respectively. Bidirectional MR analysis employed methods such as inverse variance weighted, MR-Egger, weighted median, maximum likelihood, and weighted mode. The inverse variance weighted method was primarily used to evaluate the causal relationship.
RESULTS: MR analysis in both the discovery and replication stages showed a significant causal relationship between MDD and the risk of BPH (discovery stages, odds ratio (OR) = 1.1146, 95% CI 1.0058-1.2353, P = 0.03852; replication stage, OR: 1.0042, 95% CI 1.0019-1.0065, P = 0.0004). No causal relationship was found between BPH and MDD risk in the reverse MR analysis.
CONCLUSIONS: Our findings highlight a significant association between MDD and an increased risk of BPH development. Further investigation is needed to elucidate the underlying mechanisms linking depression and BPH.

UNASSIGNED: Recent epidemiological studies have indicated a correlation between platelet indices and pulmonary arterial hypertension (PAH), yet the causality between them remains unclear. To explore the causal relationship between four platelet indices and PAH, with the aim of providing a theoretical basis for clinical prevention and treatment.
UNASSIGNED: Single-nucleotide polymorphisms (SNPs) associated with platelet-related traits were selected as exposure factors from published genome-wide association studies (GWAS), including: platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW). Summary-level data for PAH were obtained from the FinnGen study (248 cases and 289,117 controls). Two-sample and multivariable Mendelian randomization (MR) analyses were conducted to assess the causal relationship between exposure factors and the risk of outcomes. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach, supplemented by weighted median, mode-based estimation, MR-Egger regression, and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to detect and adjust for pleiotropy, ensuring the reliability of the results through sensitivity analysis.
UNASSIGNED: (1) The IVW results from the two-sample MR analysis showed a positive causal association between PLT and the risk of developing PAH [(OR = 1.649, 95%CI: 1.206-2.256, P = 0.0017)], with the sensitivity analysis confirming the robustness of the causal relationship. The MR-Egger intercept analysis did not detect potential pleiotropy (P = 0.879). (2) The MVMR results showed no statistically significant causal relationship between these four markers and the risk of developing PAH. After adjusting for collinearity, a direct positive causal association was observed between PLT and the risk of developing PAH (OR = 1.525, 95%CI: 1.063-2.189, P = 0.022).
UNASSIGNED: The positive correlation between PLT and the risk of PAH suggests that correcting elevated platelet levels may reduce the risk of developing PAH.

UNASSIGNED: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO.
UNASSIGNED: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran\'s Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses.
UNASSIGNED: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10-3), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10-3), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039).
UNASSIGNED: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO.