Bidirectional Mendelian Randomization Study Research Articles

Association between immune cells and endometrial cancer: A bidirectional Mendelian randomization study.

The prognostic significance of tumor-infiltrating immune cells in endometrial cancer is a subject of ongoing debate. Recent evidence increasingly suggests that these immune cells and cytokines, abundant in endometrial cancer tissues, play a pivotal role in stimulating the body inherent anti-tumor immune responses. Leveraging publicly accessible genetic data, we conducted an exhaustive 2-sample Mendelian randomization (MR) study. This study aimed to explore the causal links between 731 immunophenotypes and the risk of endometrial cancer. We thoroughly assessed the robustness, heterogeneity, and potential horizontal pleiotropy of our findings through extensive sensitivity analyses. Our study identified 36 immunophenotypes associated with endometrial cancer risk. Specific immunophenotypes, such as the percentage of Naive-mature B-cells in lymphocytes (OR = 0.917, 95% CI = 0.863-0.974, P = .005), and HLA DR expression on CD14-CD16 + monocytes (OR = 0.952, 95% CI = 0.911-0.996, P = .032), exhibited a negative correlation with endometrial cancer. Conversely, CD127 expression on CD45RA + CD4 + in Treg cells (OR = 1.042, 95% CI = 1.000-1.085, P = .049), and CM CD4+%T in T cell maturation stages (OR = 1.074, 95% CI = 1.012-1.140, P = .018) showed a positive correlation. Reverse MR analysis linked endometrial cancer to 4 immunophenotypes, including a positive correlation with CD127-CD8br %T cell of Treg (OR = 1.172, 95% CI = 1.080-1.270, P = .0001), and negative correlations with 3 others, including CM CD4+%T cell (OR = 0.905, 95% CI = 0.832-0.984, P = .019). Our findings underscore a significant causal relationship between immunophenotypes and endometrial cancer in bidirectional MR analyses. Notably, the CM CD4+%T immunophenotype emerged as potentially crucial in endometrial cancer development.

Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study

BackgroundPrevious observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function.MethodWe performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test.ResultsThe findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW β = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW β = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10− 6), eGFRcrea with SCF (IVW β =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10− 8), eGFRcys with GCSF (IVW β =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW β =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW β =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10− 4).ConclusionsOur findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

Genetic liability to inflammatory bowel disease is causally associated with increased risk of erectile dysfunction: Evidence from a bidirectional Mendelian randomization study

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction.Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran’s Q statistic was utilized to detect the heterogeneity.Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02–1.21, p = 0.019), and also the genetically determined Crohn’s disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02–1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92–1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity.Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn’s disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction.

A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases

ObjectivePrevious observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.MethodsWe explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results.ResultsWe found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320–2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291–2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295–1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008–1.078, p = 0.0157).ConclusionOur study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Effect of serum metabolites on the risk of iridocyclitis: a bidirectional Mendelian randomization study

Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality by analyzing pooled data from 7824 iridocyclitis patients in a Genome-Wide Association Study (GWAS) using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Employing rigorous quality control and comprehensive statistical methods, including sensitivity analyses, we examined the influence of 486 serum metabolites on iridocyclitis. Our MR analysis identified 23 metabolites with significant causal effects on iridocyclitis, comprising 17 known and 6 unidentified metabolites. Further refinement using Cochran's Q test and MR-PRESSO indicated 16 metabolites significantly associated with iridocyclitis risk. LDSC highlighted the heritability of certain metabolites, underscoring genetic influences on their levels. Notably, tryptophan, proline, theobromine, and 7-methylxanthine emerged as risk factors, while 3,4-dihydroxybutyrate appeared protective. These findings enhance our understanding of the metabolic interactions in iridocyclitis, offering insights for diagnosis, unraveling pathophysiological mechanisms, and informing potential avenues for prevention and personalized treatment.

Corrigendum: Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study

Corrigendum: Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study

Investigation of the causal association between Parkinson’s disease and autoimmune disorders: a bidirectional Mendelian randomization study

BackgroundTo date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson’s disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk.MethodsBy employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results.ResultsOur MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility.ConclusionIn general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study

BackgroundRecent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.ObjectiveWe aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.MethodsWe assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.ResultsTS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587–0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968–0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.ConclusionOur findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.

Is thyroid function associated with polycystic ovary syndrome? a bidirectional mendelian randomization study

Is thyroid function associated with polycystic ovary syndrome? a bidirectional mendelian randomization study

Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study

Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study

Causal associations of birth body size and adult body size with systemic lupus erythematosus: a bidirectional mendelian randomization study

Causal associations of birth body size and adult body size with systemic lupus erythematosus: a bidirectional mendelian randomization study

Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis

BackgroundFrailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition.MethodsInstrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results.ResultsBacteroidia (b = −0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = −0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses.ConclusionOur findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Causality between Gut Microbiota and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study

Abstract The exact relationship between inflammatory bowel disease (IBD) and gut microbiota (GM) is still unclear. This study aimed to explore the cause-and-effect relationship between IBD and GM by Mendelian randomization (MR) analysis. The IBD data used in this study were obtained from Genome-Wide Association Studies (GWAS). The GM data were from the Dutch Microbiome Project and included 207 taxa and 205 microbiota-associated pathways. Multivariate Mendelian randomization (MVMR) analysis was performed to investigate the relationship between GM and IBD. The results demonstrated that susceptibility to developing IBD is negatively correlated with class Clostridia (OR = 0.80, P = 0.003), family Sutterellacea (OR = 0.87, P = 0.014), genus Coprobacter (OR = 0.90, P = 0.009), order Clostridiales (OR = 0.80, P = 0.003), phylum Firmicutes (OR = 0.82, P = 0.002) and Coprobacter fastidiosus (OR = 0.90, P = 0.009). Conversely, the risk of developing IBD is positively correlated with the phosphopantothenate biosynthesis I pathway (OR = 1.17, P = 0.006), Bacteroides caccae (OR = 1.14, P = 0.021) and Bacteroides uniformis (OR = 1.26, P = 0.003). Reverse causality was found between the phosphopantothenate biosynthesis I pathway and IBD (OR = 1.03, P = 0.04), but not for the remaining specific GM taxa. In conclusion, our study demonstrated a causal relationship between specific GM features and IBD.

Obesity and Hypertension Mediate the Effect of Education on Deep Intracerebral Hemorrhage: A Mendelian Randomization Study

BackgroundEducational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AimTo explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. MethodsUsing summary-level Genome-wide Association Study (GWAS) data based from European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. ResultsBidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR: 0.381 [95%CI: 0.264–0.549]), deep ICH (OR: 0.334 [95%CI: 0.216–0.517]), and lobar ICH (OR: 0.422 [95%CI: 0.261–0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93% [1.20–13.45%]) and body mass index (BMI) (17.87% [3.92–34.64%]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85% [1.55–15.07%]) and BMI (18.63% [4.02–36.26%]). ConclusionThis study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.

Genetic causal relationship between multiple immune cell phenotypes and Parkinson's disease: a two sample bidirectional Mendelian randomization study.

The exact etiology of Parkinson's disease (PD), a degenerative disease of the central nervous system, is unclear. It is currently believed that its main pathological basis is a decrease in dopamine concentration in the striatum of the brain. Although many researchers have previously focused on the critical role of the immune response in PD, there has been a lack of valid genetic evidence for a causal association between specific immune cell traits and phenotypes and PD. We employed Mendelian randomisation (MR) as an analytical method to effectively assess genetic associations between exposure and outcome. Based on the largest genome-wide association study (GWAS) data to date, causal associations between multiple immune cell phenotypes and PD were validly assessed by using single nucleotide polymorphisms (SNPs), which are randomly assigned and not subject to any causality. By testing 731 immune cell phenotypes and their association with PD, the results of IVW analysis suggested that some phenotypes were considered to have a causal effect on PD(P＜0.05) . In addition, PD could have an effect on certain immunophenotypes located on Myeloid cell panel, Monocyte panel, the specific immunophenotypic results and statistical analysis values are shown in the text. The results of sensitivity analyses suggested that none of them observed the presence of horizontal pleiotropy. Our study identified a close link between immune cells and PD, and the results of this study provide ideas for the study of the immune mechanism of PD and the exploration of effective therapeutic means.

Causal relationship between intervertebral disc degeneration and osteoporosis: a bidirectional two-sample Mendelian randomization study

IntroductionThe relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated.Materials and methodsThe genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO.ResultsNo significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123–1.284, P = 8.72 × 10−8; LS-BMD: IVW, OR = 1.179, 95% CI: 1.083–1.284, P = 1.43 × 10−4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008–1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041–1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05).ConclusionOP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.

Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population

BackgroundExtensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD.MethodsTwo-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship.ResultsThe forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD.ConclusionThis MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.

Mental illness and pulmonary tuberculosis: a bidirectional two-sample Mendelian randomization study

BackgroundObservational studies have confirmed that mental illness and pulmonary tuberculosis are closely related and increase each other’s incidence; however, whether there is a causal genetic association between the two diseases remains unknown. We attempted to answer this question using bidirectional two-sample Mendelian randomization (MR) in a large cohort study.MethodWe performed a bidirectional MR analysis between mental illness (major depressive, anxiety disorder, bipolar disorder, and schizophrenia) and pulmonary tuberculosis using summary statistics from genome-wide association studies in European individuals. The inverse-variance weighted method was used as the primary analytical method to assess causality. In addition, other additional MR methods (weighted median, MR–Egger, and weighted mode) were used to supplement the inverse-variance weighted results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability.ResultWe identified no causal genetic association between mental illness and pulmonary tuberculosis after applying the inverse variance weighted method (major depressive: odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.59–1.71, P = 0.98; anxiety disorder: OR = 1.72, 95% CI = 0.05–67.67, P = 0.76; bipolar disorder OR = 0.89, 95% CI = 0.66–1.22, P = 0.48; and schizophrenia: OR = 1.05, 95% CI = 0.91–1.20, P = 0.51). Similarly, pulmonary tuberculosis was not caustically associated with mental illness (major depressive: OR = 1.01, 95% CI = 1.00–1.02, P = 0.17; anxiety disorder: OR = 1.00, 95% CI = 0.99–1.01, P = 0.06; bipolar disorder: OR = 1.02, 95% CI = 0.98–1.07, P = 0.38; and schizophrenia: OR = 1.01, 95% CI = 0.97–1.05, P = 0.66).ConclusionOur research does not support a bidirectional causal association between the aforementioned mental illnesses and pulmonary tuberculosis.

Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Socioeconomic status, personality, and major mental disorders: a bidirectional Mendelian randomization study

Previous research has suggested a correlation between socioeconomic status (SES) and mental diseases, while personality traits may be associated with SES and the risk of mental disorders. However, the causal nature of these associations remains largely uncertain. Our Mendelian randomization (MR) study aims to explore the bidirectional causality between SES and mental disorders, as well as to evaluate the potential mediating role of personality in these associations. Using bidirectional MR approach, we assessed the causality between SES indicators and mental disorders. We then used a two-step MR method to further investigate whether and to what extent personality mediates the causal associations in Caucasians. The forward MR analyses identified that years of education, household income, age at first birth and the Townsend deprivation index had a causal association with at least one mental disorder. The reverse MR analyses identified causal effects of genetically predicted schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder on five SES indicators. Importantly, mediation analysis showed that neuroticism partly mediated the causality of household income and years of education on major depressive disorder, respectively. In brief, our study confirmed the bidirectional relationship between SES and mental disorders. We also revealed the role of neuroticism in mediating the association between SES and major depressive disorder, highlighting the importance of considering both socioeconomic and personality factors in mental health research and interventions.