Inverse-variance Weighted Analysis Research Articles

Genetically predicted circulating concentrations of micronutrients and risk of autoimmune thyroiditis: a Mendelian randomized study.

Micronutrients play pivotal roles in modulating various aspects of the immune response. However, the existing literature on the association between micronutrients and autoimmune thyroiditis (AIT) remains limited and contentious. To address this gap, we conducted Mendelian randomization (MR) to investigate potential links between genetically predicted concentrations of six micronutrients (Copper (Cu), Iron (Ir), Calcium (Ca), Vitamin D (VD), Vitamin C (VC), Zinc (Zn)) and the risk of AIT. Utilizing summary statistics from genome-wide association studies (GWAS) in individuals of European descent, we employed MR methodologies to elucidate the interplay between micronutrients and AIT. Three distinct MR techniques were employed: Inverse Variance Weighted (IVW), MR-Egger regression, and Weighted Median Estimator (WME). Additionally, we evaluated outcome heterogeneity using Cochran's Q statistic and assessed pleiotropy using the MR-Egger intercept. IVW analysis revealed no substantial evidence supporting a significant impact of genetically predicted micronutrient concentrations on AIT risk (Cu: OR = 0.918, P = 0.875; Ir: OR = 0.653, P = 0.264; Ca: OR = 0.964, P = 0.906; VD: OR = 0.717, P = 0.378; VC: OR = 0.986, P = 0.875; Zn: OR = 0.789, P = 0.539). Cochran's Q test for IVW indicated no notable heterogeneity. Moreover, the MR-Egger intercept method suggested the presence of horizontal pleiotropy between serum VC levels and AIT (MR-Egger intercept = -0.037, p = 0.026), while no such pleiotropy was observed for other micronutrients. Our MR analysis does not support a causal relationship between genetically predicted concentrations of six micronutrients (Cu, Ir, Ca, VD, VC, and Zn) and the risk of AIT.

Abdominal multi-organ iron content and the risk of Parkinson's disease: a Mendelian randomization study.

To evaluate the causal relationship between abdominal multi-organ iron content and PD risk using publicly available genome-wide association study (GWAS) data. We conducted MR analysis to assess the effects of iron content in various abdominal organs on PD risk, followed by reverse analysis. Additionally, MVMR analysis evaluated the independent effects of organ-specific iron content on PD. We utilized genetic variation data from the UK Biobank, including liver iron content (n = 32,858), spleen iron content (n = 35,324), and pancreas iron content (n = 25,617), as well as summary-level data for Parkinson's disease from the FinnGen (n = 218,473) and two other large GWAS datasets of European populations (First dataset n = 480,018; Second dataset n = 2,829). The primary MR analysis used the inverse variance-weighted (IVW) method, confirmed by MR-Egger and weighted median methods. Sensitivity analysis was performed to address potential pleiotropy and heterogeneity. Observational cohort results were validated through replication cohort analysis, followed by meta-analysis. IVW analysis revealed a causal relationship between increased liver iron content and elevated risk of PD (OR = 1.27; 95% CI: 1.05-1.53; p = 0.015). No significant causal relationship was observed between spleen (OR = 1.00; 95% CI: 0.76-1.32; p = 0.983) and pancreatic (OR = 0.93; 95% CI: 0.72-1.20; p = 0.573) iron content and increased risk of PD. Meta-analysis of GWAS data for PD from three different sources using the random-effects IVW method showed a statistically significant causal relationship between liver iron content and the occurrence of PD (OR = 1.17, 95% CI: 1.01-1.35; p = 0.012). This study presents evidence from Mendelian randomization (MR) analysis indicating a significant causal link between increased liver iron content and a higher risk of Parkinson's disease (PD). These findings suggest that interventions targeting body iron metabolism, particularly liver iron levels, may be effective in preventing PD.

A two sample mendelian randomization analysis investigates causal effects between gut microbiome and immune related Vasculitis

Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

Causal association between brain structure and obstructive sleep apnea: A mendelian randomization study

ObjectivePrevious studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship. MethodsFirstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. ResultsThe results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates. ConclusionsThis study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

Association of partial infections with the risk of psoriasis: A two-sample Mendelian randomization study.

As a common chronic recurrent inflammatory skin disease, psoriasis is characterized by erythema and scaly skin lesions, with infection as an integral part of the pathogenesis of many diseases. Many previous cases reported the impact of psoriasis on infection. However, the existing research fails to completely clarify the infection factors associated with the potential of these diseases and causality. Thirteen kinds of pathogens and their immune responses and psoriasis in the phenotype of 46 species of SNPs data were respectively obtained from the GWAS catalog database and the UK biobank database. With the help of R software, three methods of inverse variance weighted (IVW), weighted median (WME), and MR-Egger regression were used to analyze the causality of the dataset. According to the results of IVW analysis, there is a causal relationship between anti-Epstein Barr virus antibody and psoriasis (OR: 1.003, 95% CI: 1.001∼1.006, P=0.046) with a positive correlation. Based on the results of MR analysis, there is a causal relationship between psoriasis and EBV infection, which indicates that EBV infection can increase the risk or severity of psoriasis. Therefore, in clinical scenarios, patients afflicted with psoriasis should be prevented from contracting the infection and recurrence of EBV as well as symptoms of psoriasis. The underlying immunological mechanism also provides a new perspective for experimental research.

Association between inflammatory cytokines and prostate cancer

IntroductionWe conducted bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between 91 inflammatory cytokines and prostate cancer (PCa).Material and methodsThe Inverse Variance Weighted (IVW) model served as the primary two-sample MR analysis method, utilized to estimate the causal effect of exposure on the outcome. The Weighted Median (WM) and MR Egger methods were additionally employed to complement the IVW model. Sensitivity analyses were performed using Cochran's Q test for both the IVW and MR Egger methods. To assess the presence of horizontal pleiotropy, the instrumental variables (IVs) were subjected to the MR-Egger intercept test.ResultsFollowing Bonferroni correction, the IVW analysis revealed positive correlations between PCa and the levels of C-C motif chemokine 20 (CCL20), C-C motif chemokine 23 (CCL23), fibroblast growth factor 19 (FGF19), fibroblast growth factor 23 (FGF23), and interleukin-6 (IL-6). Notably, IL-6 exhibited the strongest positive association effect (odds ratio [95% confidence interval]: 1.0076 [1.0014, 1.0139]), followed by CCL-20 (1.0067 [1.0004, 1.0129]) and FGF23 ([1.0002, 1.0119]). Reverse MR analysis indicated a negative causal relationship between PCa and interleukin-22 receptor subunit alpha-1 levels (IL22RA1) (0.4852 [0.2390, 0.9847]).ConclusionsThis study proposes that there exists a positive correlation between the levels of CCL20, CCL23, FGF19, FGF23, and IL-6 and the occurrence of PCa. Furthermore, we found evidence to support the causal relationship between decreased levels of IL22RA1 and the development of PCa. These findings unveil novel biomarkers and pathways that could potentially be targeted for the prevention and clinical treatment of PCa.

Genetically predicted allergic rhinitis causally increases the risk of erectile dysfunction.

Evidence shows that allergic rhinitis (AR) may increase the risk of erectile dysfunction (ED). This study aims to investigate whether there is a causal relationship between AAR and ED by Mendelian randomization (MR) analysis. We performed a two-sample MR analysis using genome-wide association studies (GWAS) summary data. Single nucleotide polymorphisms (SNPs) associated with AR and ED were obtained from the GWAS database. The MR analysis primarily employed the inverse variance weighted (IVW), MR Egger, and weighted median (WM) methods. We assessed pleiotropy using the MR-PRESSO global test and MR-Egger regression. Cochran's Q test was used to evaluate heterogeneity, and a leave-one-out analysis was performed to verify the robustness and reliability of the results. The IVW analysis demonstrated a positive association between genetic susceptibility to AR and an elevated relative risk of ED (IVW OR = 1.40, p = 0.01, 95% CI 1.08-1.80). The results obtained from MR-Egger regression and WM methods exhibited a consistent trend with the results of the IVW method. Sensitivity analyses showed no evidence of heterogeneity nor horizontal pleiotropy. The leave-one-out analysis showed that the findings remained robust and were unaffected by any instrumental variables. This study presents genetic evidence that indicates a causal association between AR and ED.

Causality between major depressive disorder and functional dyspepsia: a two-sample Mendelian randomization study.

To investigate the causal relationship between major depression and functional dyspepsia using two-sample Mendelian randomization. Data for major depression and functional dyspepsia were obtained from genome-wide association studies. We selected Single Nucleotide Polymorphisms (SNPs) strongly associated with severe depression. Mendelian randomization analysis was conducted using methods such as Inverse-Variance Weighted (IVW), MR-Egger, and Weighted Median Estimator (WME). Sensitivity analysis was performed to assess the robustness of the results. A total of 31 eligible SNPs were identified as instrumental variables for major depression. IVW analysis indicated a positive causal relationship between the two conditions (β = 0.328; SE = 0.137; p = 0.017), suggesting that severe depression increases the risk of functional dyspepsia (OR = 1.389; 95% CI: 1.062-1.816). Sensitivity tests showed no evidence of heterogeneity or horizontal pleiotropy (p > 0.05). MR analysis had shown that major depressive disorder is associated with an increased risk of functional dyspepsia.

Causal relationships between COVID-19 and venous thromboembolism: A mendelian randomization analysis.

Objective: Observational studies show the correlation between COVID-19 and venous thromboembolism (VTE) risk. However, the causal effects remain uncertain. We aimed to explore the potential causal association between COVID-19 and VTE using Mendelian randomization (MR) design. Methods: Two-sample MR was used to evaluate the potential causality between COVID-19 and VTE by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The weighted median, MR-Egger, simple mode, and weighted mode were employed as supplementary methods for MR estimations, with the inverse-variance weighted (IVW) method serving as the principal analysis. In addition, we took sensitivity analyses, including Cochran's test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to ensure that we obtained stable and reliable results. Results: Our study selected 26 COVID-19 severity, 31 COVID-19 hospitalization, and 13 COVID-19 susceptibility SNPs as instrumental variables. The IVW analysis results revealed that there was no causal relationship between COVID-19 severity, hospitalization, or susceptibility and VTE, with odds ratios of 0.974 (95%CI: 0.936-1.013, p = 0.19), 0.976 (95%CI: 0.918-1.039, p = 0.447), and 0.908 (95%CI: 0.775-1.065, p = 0.235), respectively. The IVW approach yielded consistent results with MR-Egger, Weighted Median simple mode, and weighted mode. MR-PRESSO and sensitivity analysis further confirmed the stability and consistency of the MR results. Conclusions: This study did not find evidence to support a causal relationship between COVID-19 and VTE at the genetic level. Further investigation is warranted to determine if the significant association reported in previous observational studies between the two is due to confounding factors.

Potential causal association between serum vitamin D levels and intervertebral disc degeneration: A mendelian randomization study

ObjectivesIntervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial implications for disability and healthcare expenditures. The role of serum vitamin D (25-Hydroxyvitamin D, 25(OH)D) levels in the pathogenesis of various musculoskeletal conditions has been explored in prior observational studies, suggesting a potential association. While previous observational studies have suggested an association between the two conditions, it might confound the effect of 25(OH)D on IDD. This Mendelian randomization (MR) study seeks to elucidate the causal relationship between 25(OH)D and IDD. MethodsWe performed a MR analysis using summary-level data from genome-wide association studies (GWAS) of 25(OH)D (sample size = 441,291 European) and IDD (sample size = 336,439 (cases = 41,669, controls = 294,770) European). Single nucleotide polymorphisms (SNPs) significantly associated with 25(OH)D (p < 5 × 10−8) were selected as instrumental variables. The associations between genetically predicted 25(OH)D and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings. ResultsIn the primary IVW analysis, genetically predicted 25(OH)D was unrelated associated with IDD (odds ratio (OR) = 0.9671, 95% confidence interval (CI): 0.8956–1.0444, p = 0.39). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.64). ConclusionsThis study found no obvious evidence that 25(OH)D is causally associated with IDD risks. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Dried fruit intake and lower risk of type 2 diabetes: a two-sample mendelian randomization study

BackgroundPrevious studies have shown controversy about whether dried fruit intake is associated with type 2 diabetes. This study aimed to examine the potential causal effect of dried fruit intake on type 2 diabetes by conducting a two-sample Mendelian randomization study.MethodsWe used genome-wide association study (GWAS) summary statistics for MR analysis to explore the causal association of dried fruit intake with T2D. The inverse-variance weighted (IVW) method was used as the main analytical method for MR analysis. In addition, the MR-Egger method and the weighted median method were applied to supplement the IVW method. Furthermore, Cochrane’s Q test, MR-Egger intercept test, and leave-one-out analysis were used to perform sensitivity analysis. The funnel plot was used to assess publication bias.ResultsThe results from the IVW analysis indicated that dried fruit intake could reduce the risk of T2D [odds ratio (OR) = 0.392, 95% confidence interval (CI): 0.241–0.636, p-value = 0.0001]. In addition, the result of additional method Weighted median is parallel to the effects estimated by IVW. Furthermore, the sensitivity analysis illustrates that our MR analysis was unaffected by heterogeneity and horizontal pleiotropy. Finally, the results of the leave-one-out method showed the robustness of our MR results. And the funnel plot shows a symmetrical distribution.ConclusionOur study provides evidence for the benefits of dried fruit intake on T2D. Therefore, a reasonable consumption of dried fruit may provide primary prevention.

No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study.

We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain. Two-sample MR study. We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks. Genetic instrumental variables were taken from an exposure GWAS of CRP (n=204,402). Outcome GWASs examined spinal pain (n=1,028,947), extent of multisite chronic pain defined as the number of locations with chronic pain (n=387,649), and chronic widespread pain (n=249,843). We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis and sensitivity analyses using other methods. We calculated odds ratios (ORs), 95% confidence intervals (95% CIs), and p-values, using a Bonferroni correction (p<0.0166) to account for 3 primary comparisons. Greater serum CRP (mg/L) was not significantly causally associated with spinal pain (OR=1.04, 95% CI 1.00-1.08; p=0.07) in IVW analysis. Greater serum CRP also showed no significant causal association with extent of multisite chronic pain in IVW analysis (beta coefficient= 0.014, standard error=0.011; p=0.19). CRP also showed no significant causal association with chronic widespread pain in IVW analysis (OR=1.00, 95% CI 1.00-1.00; p=0.75). All secondary and sensitivity analyses also showed no significant associations. This MR study found no causal association of CRP on spinal pain, the extent of chronic pain, or chronic widespread pain. Future studies examining mechanistic biomarkers for pain conditions should consider other candidates besides CRP.

Hidradenitis suppurativa and cardiovascular diseases: A bidirectional Mendelian randomization study.

Prior investigation has indicated a link between Hidradenitis suppurativa (HS) and cardiovascular diseases (CVDs), yet the causal relationship (CR) between these conditions remains unresolved. This investigation utilized bidirectional Mendelian randomization (MR) analysis to determine the CR between HS and CVDs. Genetic instruments for both conditions were sourced from genome-wide association studies (GWAS). The GWAS summary data for CVD comprised coronary artery disease (CAD), myocardial infarction (MI), coronary atherosclerosis (CA), ischemic stroke (IS), and chronic heart failure (CHF). Four new approaches were added to the inverse variance weighted (IVW) method for the main analysis: weighted median, weighted MR-Egger, simple mode, and weighted mode. The validity of the causal conclusions was verified by sensitivity tests that included leave-one-out analysis, heterogeneity, and pleiotropy. HS and CAD (OR=1.024; 95%CI: 1.002-1.046, P=0.033), MI (OR=1.001; 95%CI: 1.000-1.002, P=0.033), and CA (OR=1.001; 95%CI: 1.000-1.002, P=0.022) were identified to have a positive CR, according to the IVW analysis. Conversely, no significant association was identified between HS and either IS or CHF. Furthermore, the bidirectional analysis indicated no reverse causation between these diseases. The findings of this study suggest a potential CR between HS and CAD, MI, and CA. Additional research is warranted to elucidate the biological mechanisms underlying these associations.

Dissecting the causal role of immunophenotypes in primary sclerosing cholangitis risk: A Mendelian randomization study.

Primary sclerosing cholangitis (PSC), a chronic cholestatic liver condition, is frequently associated with inflammatory bowel disease. Specific immune cells have been implicated in PSC pathogenesis with the emergence of the "microbiota" and "gut lymphocyte homing" hypotheses, albeit their identities remain controversial. The first genome-wide association analysis leveraged nonoverlapping data from 3757 Europeans to evaluate 731 immunophenotypes. A genome-wide association analysis comprising 2871 cases and 12,019 controls yielded summary statistics for PSC. An inverse-variance weighted (IVW) analysis was performed to identify immunophenotypes causally related to PSC, and the results were validated using weighted mode, MR-Egger, and weighted median methods. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. IVW analysis revealed 26 immune traits exhibiting causal associations with PSC. CD3 on HLA-DR+ CD4+ (IVW odds ratio [OR]: 0.904; 95% confidence interval [CI]: 0.828-0.986, P = .023) and CD3 on secreting Treg (IVW OR: 0.893; 95% CI: 0.823-0.969, P = .007) were negatively associated with PSC susceptibility and demonstrated high consistency across the 3 validation methods. Moreover, 7 other immune traits, including CD39+ resting Treg absolute cell (IVW OR = 1.083, 95% CI: 1.013-1.157, P = .019), CD39+ secreting Treg absolute cell (IVW OR = 1.063, 95% CI: 1.012-1.118, P = .015), CD3 on naive CD8br (IVW OR = 0.907, 95% CI: 0.835-0.986, P = .022), CD3 on CD39+ activated Treg (IVW OR = 0.927, 95% CI: 0.864-0.994, P = .034), CD28 on resting Treg (IVW OR = 0.724, 95% CI: 0.630-0.833, P = 5.95E-06), and CD39 on CD39+ CD4+ (IVW OR = 1.055, 95% CI: 1.001-1.112, P = .044) exhibited consistent results in the Weighted Median and Weighted Mode validation methods. Moreover, no significant heterogeneity or horizontal pleiotropy was observed across the single nucleotide polymorphisms. The leave-one-out results revealed that sequentially eliminating each single nucleotide polymorphism had no significant influence on model effect estimates or qualitative inference. This study evaluated potential causal links between 731 immune traits and PSC susceptibility. Twenty-six immune traits were identified using the IVW method. Verification across multiple methods revealed 9 immune traits with a plausible causal connection to PSC. These findings may uncover mechanistic pathways and novel therapeutic approaches.

Assessing causal associations of bile acids with obesity indicators: A Mendelian randomization study.

Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity may be intricately linked to BAs and their conjugated compounds. Our study aims to assess how BAs influence the obesity indicators by Mendelian randomization (MR) analysis. Instrumental variables of 5 BAs were obtained from public genome-wide association study databases, and 8 genome-wide association studies related to obesity indicators were used as outcomes. Causal inference analysis utilized inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analysis involved MR-PRESSO and leave-one-out techniques to detect pleiotropy and outliers. Horizontal pleiotropy and heterogeneity were assessed using the MR-Egger intercept and Cochran Q statistic, respectively. The IVW analysis revealed an odds ratio of 0.94 (95% confidence interval: 0.88, 1.00; P = .05) for the association between glycolithocholate (GLCA) and obesity, indicating a marginal negative causal association. Consistent direction of the estimates obtained from the weighted median and MR-Egger methods was observed in the analysis of the association between GLCA and obesity. Furthermore, the IVW analysis demonstrated a suggestive association between GLCA and trunk fat percentage, with a beta value of -0.014 (95% confidence interval: -0.027, -0.0004; P = .04). Our findings suggest a potential negative causal relationship between GLCA and both obesity and trunk fat percentage, although no association survived corrections for multiple comparisons. These results indicate a trend towards a possible association between BAs and obesity, emphasizing the need for future studies.

Association of circulating minerals and vitamins with pregnancy complications: a Mendelian randomization study.

Though considerable studies suggesting connections between micronutrients and pregnancy complications, current evidence remains inconsistent and lacks causative confirmation. Our study aimed to explore the causal links between them with a two-sample Mendelian randomization (MR) analysis. Genome-wide association studies (GWAS) data for circulating micronutrients were sourced from GWAS Catalog consortium and PubMed, while data for pregnancy outcomes, including gestational diabetes mellitus (GDM), gestational hypertension (GH), spontaneous abortion (SA), preterm birth (PTB), and stillbirth (SB), were retrieved from the UK Biobank and FinnGen consortia. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger, followed by sensitivity analyses and meta-analysis for validation. Genetically predicted higher vitamin E (OR = 0.993, 95% CI 0.987-0.998; p = 0.005) levels were inversely associated with SA risk. Consistent results were obtained in meta-analysis (OR = 0.99, 95% CI 0.99-1.00; p = 0.005). Besides, a potential positive causality between genetic predisposition to vitamin B12 and SB was identified in both IVW (OR = 0.974, 95% CI 0.953-0.996; p = 0.018) and WM analysis (OR = 0.965, 95% CI 0.939-0.993; p = 0.013). However, no causal relationships were observed between other analyzed circulating micronutrients and pregnancy complications. This study offers compelling evidence of causal associations between circulating levels of vitamins E, B12 and the risk of SA and SB, respectively. These findings are pivotal for pregnancy complications screening and prevention, potentially guiding clinical practice and public health policies toward targeted nutritional interventions.

Mendelian randomization study on association between grip strength and BMD in different age groups

IntroductionThis study aimed to use the Mendelian randomization study method to verify the causal relationship between grip strength and bone mineral density (BMD) in different ages and different parts of the body.Materials and methodsThe analysis was based on pooled data from genome-wide association studies (GWAS). Hand grip strength (right) was used as the exposure variable and total body bone mineral density (BMD) of different age groups was used as the outcome variable. Single-nucleotide polymorphisms highly correlated with exposure variables were used as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis method, and the Mendelian randomization Egger (MR-Egger) regression and weighted median methods were used as supplementary evidence for the IVW results. Horizontal pleiotropy and heterogeneity tests were conducted to ensure the stability of the results.ResultsAnalyzing the GWAS data on osteoporosis as the outcome variable, the IVW analysis showed that osteoporosis risk was associated with decreased grip strength in the 45–60 age group and the risk of declining lumbar spine BMD was associated with decreased grip strength. However, there was no significant correlation between the risk of osteoporosis in other age groups and changes in grip strength.ConclusionA causal relationship exists between decreased grip strength and osteoporosis risk in people aged 45–60 years. The risk of BMD declining in the lumbar spine was associated with reduced grip strength.

The relationship between periodontal disease and gastric cancer: A bidirectional Mendelian randomization study.

Previous observational studies have suggested a possible association between periodontal disease and gastric cancer (GC); however, a causal relationship has not yet been established. This study aimed to explore the causal relationship between the 2 through a 2-sample bidirectional Mendelian randomization (MR) study. Genome-wide association studies (GWAS) summary statistics were obtained from publicly available GWAS and relevant databases. Two-sample bidirectional MR analysis was conducted to investigate the causal relationship between periodontal disease and GC using the inverse-variance weighted (IVW) method selected as the primary analytical approach. Cochran Q test, MR-PRESSO, MR-pleiotropy, and leave-one-out analyses were performed to assess heterogeneity, pleiotropy, and sensitivity. In European ancestry, IVW analysis revealed no causal relationship between periodontal disease and GC (OR = 1.873; 95% CI [4.788e-10, 7.323e + 09]; P = .956), or between loose teeth and GC (OR = 1.064; 95% CI [0.708, 1.598]; P = .765). In East Asian ancestry, there was no causal relationship between periodontitis and GC according to IVW (OR = 0.948; 95% CI [0.886, 1.015]; P = .126). Conversely, according to the results of the IVW analysis, there was no causal relationship between GC and periodontal disease, regardless of European or East Asian ancestry. Furthermore, there was no heterogeneity or pleiotropy in the causal relationships between these variables (all P > .05), suggesting a certain level of reliability in our results. Within the limitations of this MR study, we found no mutual causal relationship between periodontal disease and GC. This finding can prevent overtreatment by clinical physicians and alleviate the psychological burden on patients.

Causal effect of immune cells on idiopathic pulmonary fibrosis: A mendelian randomization study

BackgroundA key component of idiopathic pulmonary fibrosis (IPF) is the involvement of immune cells. However, the causal interaction between different immune cell signatures and IPF remain inconclusive. ObjectivesBased on publicly accessible data, our study utilized the Mendelian randomization (MR) approach to determine the causative relevance of complex immune cell phenotypes in IPF. MethodsWe deployed a two-sample Mendelian randomization approach to evaluate the causal interaction between immune cell markers and IPF. All data regarding 731 immune signatures and IPF were acquired from two genome-wide association studies (GWAS) that are accessible to the public. The original study adopted the inverse variance weighted (IVW) method, followed by sensitivity analyses aimed at eliminating heterogeneity and pleiotropy. Additionally, Multivariate Mendelian randomization (MVMR) was utilized to identify the independent risk factors in our study. ResultsThe summary dataset for IPF was accessed from the Finnish Genetic Consortium R9, comprising 2018 patients and 373,064 controls. And the dataset for immune signatures was conducted in 3,757 Sardinian individuals. By conducting IVW and extensive sensitivity analyses, univariate Mendelian randomization (UVMR) identified one immunophenotype that remained causally associated with IPF after false discovery rate (FDR) correction: CD39 on CD39+ CD8+T cells (odd ratio [OR] = 0.850, 95 % confidence interval [CI] = 0.787–0.918, P = 3.68 × 10−5). The causal association with IPF was further validated using MVMR. ConclusionsBased on rigorous MR analysis methods and FDR correction, our study demonstrated that CD39 on CD39+ CD8+T cells showed a protective effect against IPF, providing effective insights for preventing and diagnosing pulmonary fibrosis.

Liposomes have a direct effect on multiple myeloma: a Mendelian randomization study.

Multiple myeloma (MM), a malignant disease of plasma cells originating in the bone marrow, is influenced significantly by genetic factors. Although plasma liposomes have been linked to MM, the nature of their potential causal relationship remains to be elucidated. This study aims to explore this relationship using Mendelian randomization (MR) analysis. Liposome-associated genetic instrumental variables (IVs) were identified from plasma lipidomics data of 7,174 Finnish individuals within a Genome-Wide Association Study (GWAS) pooled database. A MM pooled dataset was sourced from a GWAS meta-analysis encompassing 150,797 individuals, including 598 MM patients and 218,194 controls. These IVs underwent MR analysis, adhering to strict criteria for correlation, independence, and the exclusion of confounders. The inverse variance weighted (IVW) method, MR-Egger method, weighted median (WM) method, and simple median were utilized for MR analysis assessment, alongside Cochran's Q test, MR-Egger intercept, MR-Pleiotropy Residual Sum and Outlier (MR-RESSO) method, and leave-one-out analysis for evaluating heterogeneity, multiplicity, and instrumental bias. The study identified 88 significant, independent single nucleotide polymorphisms (SNPs) as IVs for MR analysis, each with an F-statistic value above 10, indicating robustness against weak instrument bias. IVW analysis revealed associations between six plasma liposome components and MM risk (p < 0.05). Phosphatidylinositol (16:0_18:1) serum levels (odds ratio [OR] = 1.769, 95% confidence interval [CI]: 1.132-2.763, p = 0.012) and triacylglycerol (56:4) levels (p = 0.026, OR = 1.417, 95% CI: 1.042-1.926) were positively correlated with the risk of multiple myeloma development. Phosphatidylethanolamine (18:0_20:4) (p = 0.004, 95% CI: 0.621-0.916, OR = 0.754), phosphatidylcholine (18:2_20:4) (p = 0.004, OR = 0.680, 95% CI: 0.519-0.889), sterol ester (27:1/18:3) levels (p = 0.013, OR = 0.677, 95% CI: 0.498-0.922), and phosphatidylcholine (O-18:2_20:4) levels (OR = 0.710, 95% CI: 0.517-0.913, p = 0.033) were negatively associated with the risk of developing multiple myeloma. The Cochran's Q test did not detect statistical method heterogeneity, nor did the MR-RESSO test or the MR-Egger intercept detect horizontal pleiotropy; leave-one-out analyses confirmed the absence of bias from individual SNPs. Our findings suggest a complex relationship between plasma liposome components and MM risk. Elevated serum levels of triacylglycerol and phosphatidylinositol are positively associated with MM risk, while certain phospholipids and sterol esters offer a protective effect. This study provides valuable insights into the clinical relevance of liposomes in the pathology of multiple myeloma.