Simple Mode Research Articles

Causal relationship between dietary intake and IgA nephropathy: a Mendelian randomization study.

Previous studies have reported that dietary intake is associated with immunoglobulin A nephropathy (IgAN). However, the causal relationship remains unknown. Based on publicly available genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between 26 dietary exposures and IgAN. Five methods, including inverse variance weighting (IVW), MR-Egger regression, weighted median, simple mode, and weighted mode, were applied in the MR analysis. To identify the presence of horizontal pleiotropy, we used the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test. Cochran's Q statistics were used to assess instrument heterogeneity. We conducted sensitivity analysis using the leave-one-out method. Finally, the results indicated alcohol intake frequency (odds ratio [OR] (95% confidence interval [CI]) = 1.267 (1.100-1.460), p = 0.0010295) was a risk factor of IgAN, while cheese intake (OR (95% CI) = 0.626 (0.492-0.798), p = 0.0001559), cereal intake (OR (95% CI) = 0.652 (0.439-0.967), p = 0.0334126), and sushi intake (OR (95% CI) = 0.145 (0.021-0.997), p = 0.0497) were protective factors of IgAN. No causal relationship was found between IgAN and the rest of the dietary exposures. Our study provided genetic evidence that alcohol intake frequency was associated with an increased risk of IgAN, while cheese, cereal, and sushi intake were associated with a decreased risk of IgAN. Further investigation is required to confirm these results.

Elucidating the role of hepatic enzymes in spontaneous abortion: a Mendelian randomization approach.

While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA. Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis. The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899). The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA.

Causal associations between gut microbiota and premature rupture of membranes: a two-sample Mendelian randomization study.

Previous study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate. A two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium's largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses. The IVW method revealed that class Mollicutes (IVW, OR=0.773, 95%CI: 0.61-0.981, pval = 0.034), genus Marvinbryantia (IVW, OR=00.736, 95%CI: 0.555-0.977, pval = 0.034), genus Ruminooccaceae UCG003 (IVW, OR=0.734, 95%CI: 0.568-0.947, pval = 0.017) and phylum Tenericutes (IVW, OR=0.773, 95%CI: 0.566-1.067, pval = 0.034) were associated with a reduced risk of PROM, while genus Collinsella (IVW, OR=1.444, 95%CI: 1.028-2.026, pval = 0.034), genus Intestinibacter (IVW, OR=1.304, 95%CI: 1.047-1.623, pval = 0.018) and genus Turicibacter (IVW, OR=1.282, 95%CI: 1.02-1.611, pval = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (pval=0.045), genus Lachnoclostridium should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (pval >0.05). In this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.

Mendelian randomization identifies causal associations between GWAS-associated bacteria and their metabolites and rheumatoid arthritis.

Accumulating evidence suggests that an imbalance of gut microbiota is commonly observed in patients with rheumatoid arthritis (RA). However, it remains unclear whether gut microbiota dysbiosis is a cause or consequence of RA, and the mechanisms by which gut dysbiosis contributes to RA have not been fully understood. This study aimed to investigate the causal relationship between gut microbiota and metabolites with RA. A two-sample Mendelian randomization analysis was performed to estimate the causality of gut microbiota and metabolites on RA. A genome-wide association study (GWAS) of 211 gut microbiota and 217 metabolites was used as the exposure, whereas RA was treated as the outcome. Inverse variance weighted (IVW) was regarded as the primary approach for calculating causal estimates. MR Egger method, Weighted median method, Simple mode method, and weighted mode method were used for sensitive analysis. Metabolic pathway analysis was performed via the web-based Metaconflict 5.0. Additionally, an animal study was undertaken to evaluate the results inferred by Mendelian randomization. This study indicated that six gut microbiota taxa (RuminococcaceaeUCG013, Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, Clostridia, and Veillonellaceae) were estimated to exert a positive impact on RA. Conversely, seven gut microbiota taxa (Oxalobacter, Cyanobacteria, RuminococcaceaeUCG002, LachnospiraceaeUCG010, Christensenellaceae, Oxalobacteraceae, Anaerostipes) were estimated to exert a negative impact on RA. Three metabolites, namely indole-3-propionate (IPA), glycine and sphingomyelin (SM 16:1), were found to be linked to lower RA risk, while five metabolites (argininosuccinate, CE 20_4, TAG 58_8, PC 40_6, and LPC 20_4) were linked to higher RA risk. Additionally, four metabolic pathways were identified by metabolic pathway analysis. The collagen-induced arthritis (CIA) rats exhibited a higher relative abundance of Class_Clostridia and a lower abundance of Genus_Lachnospiraceae (p < 0.05) than the healthy controls. This study identified causal associations between specific gut microbiota, metabolites, and RA. These findings support the significant role of gut microbiota and metabolites in RA pathogenesis.

A cause-effect relationship between uterine diseases and breast cancer: A bidirectional Mendelian randomization study

ObjectiveTo explore the cause-effect relationship between uterine diseases (UDs) and breast cancer (BC) and underlying mechanism of the cause-effect relationship, enhance understanding of the association between BC and UDs. MethodsA two-sample bidirectional Mendelian randomization (MR) analysis was conducted. We obtained summary statistics data from GWAS for BC, endometriosis, endometrial cancer (EC), uterine leiomyoma (UL), uterine polyps (UP), and cervical cancer (CC). Independent SNPs were selected as instrumental variables (IVs) for each disease. The inverse variance weighted (IVW) method was primary used for estimating the causal association between UDs and BC. To further evaluate the consistency and dependability of the results, we also utilized the weighted median, weighted mode, simple mode, and MR-Egger methods, along with sensitivity analyses. Furthermore, a supplementary analysis focusing on the variants linked to BC and UDs was conducted. This involved identifying corresponding genes and subsequently performing KEGG/GO analyses to investigate potential molecular mechanisms. ResultsThe results indicated significant associations between genetic susceptibility to endometriosis, EC, and UL with BC risk. The odds ratios (ORs) were as follows: endometriosis at 0.963 (95 % CI, 0.942–0.984; p = 7.11e-5), EC at 1.056 (95 % CI, 1.033–1.081; p = 2.39e-6), and UL at 1.027 (95 % CI, 1.006–1.048; p = 0.010). Conversely, the predisposition to BC inferred from genetic factors was markedly correlated with an elevated risk of EC indicated by an OR of 1.066 (95 % CI, 1.019–1.116; p = 0.006), and was correlated with UP risk (OR, 1.001,95 % CI, 1.000–1.002; p = 0.001).Sensitivity analyses provided weak evidence for these effects, suggesting that the study's outcomes are consistent and trustworthy. Further analysis of the genetic variants associated with BC, and these related genes are enriched in Cellular senescence, GnRH secretion, Phosphatidylinositol signaling system, and so on. ConclusionThis study corroborates the existence of a reciprocal causal relationship between BC and EC, as well as highlighting the substantial correlations between a genetic susceptibility to UL and endometriosis with BC. BC may exert their influence on EC and UP through Cellular senescence, GnRH secretion, and other pathways. These discoveries offer fresh perspectives on the genetic pathogenesis of BC and UDs, and can guide future experimental studies. Additionally, they lay down a groundwork for the development of tailored preventative and therapeutic strategies moving forward.

Causality of Hashimoto's Thyroiditis to Thyroid Cancer: A 2-S Mendelian Randomization Study

BackgroundObservational studies have indicated an association between Hashimoto's thyroiditis (HT) and the risk of thyroid cancer (TC); however, the causality and direction of these effects in genetics remain unclear. Therefore, our study aims to investigate the relationship between genetic susceptibility to HT and TC through a bidirectional Mendelian randomization (MR) approach using twin samples. MethodsMR analysis was conducted using genetic instruments associated with HT, selected from a comprehensive genome-wide association meta-analysis involving a total of 756 000 individuals of European and East Asian descent. The data set for TC comprised 1.486 million individuals, including both European and East Asian populations. Single nucleotide polymorphisms closely linked to HT were derived from genome-wide association studies. Two-sample bidirectional MR analyses were applied to assess the causal association between HT and TC, using inverse-variance weighted methods, and MR Egger, weighted median, simple mode, and weighted mode. Furthermore, sensitivity analyses were conducted employing the MR-Egger regression model, weighted median method, MR pleiotropy residual sum and outlier, and leave-one-out technique. ResultsMR analyses revealed no evidence of a causal relationship between HT and TC in either European or East Asian populations (all P > .1). However, bidirectional MR analysis demonstrated a causal relationship between TC and HT in the European population (odds ratio = 1.0838, 95% confidence interval: 1.0346, 11 354, P = .000686). ConclusionThis MR analysis indicates a lack of evidence supporting an association between genetically predicted HT and the risk of developing TC. In contrast, there is evidence of a causal relationship between genetically predicted TC and HT.

Causal inference between physical activity and chronic diseases: Insights from a two-sample Mendelian randomization study

Chronic diseases are major causes of global death and disability, significantly impacting individual health and imposing economic burdens. This study aims to investigate the causal relationship between physical activity (PA) and the development of chronic diseases. Using a Mendelian randomization (MR) approach, we incorporated average PA and its subtypes (more than 450 ​000 participants) as exposure measures and eight chronic diseases as outcome measures. Data were obtained from the European Genome-Wide Association Study (GWAS). The primary causal analysis technique employed was the inverse variance weighting (IVW) method, with MR-Egger, weighted median, weighted mode, and simple mode used to validate the results. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. The IVW approach results show that vigorous physical activity (VPA) is associated with a modest reduction in the risk of major coronary heart disease (OR ​= ​0.95, 95% CI: 0.91–0.99, p ​= ​0.01). The causal directions of the other four MR methods are consistent with this result and validated by sensitivity analysis. No substantial associations were found between other levels of PA and chronic disease. Our findings underscore the importance of VPA in preventive cardiology and suggest its potential role in public health initiatives. Further research should explore the impact of PA on different demographic groups and the dose-response relationship of VPA on heart health.

Controlling factors of Riedel shear spacing in the simple shear mode of strike-slip fault: Insights from sandbox models

Strike-slip faults generally develop Riedel shears (R-shears), which exhibit parallel and evenly-spaced distribution characteristics. However, the factors controlling the R-shear spacing in strike-slip faults are still unclear. The influence of material properties such as internal friction angle and cohesion, basal friction, and the thickness of brittle layers (T) on the R-shear spacing (S) are investigated using analogue models in this paper. Research findings indicate that the internal friction angle of the material and the thickness of the brittle layer have a significant impact on the R-shear spacing, with the thickness of the brittle layer directly determining the R-shear spacing as evidenced by their linear correlation. In comparison, cohesion and basal friction have insignificant effects on R-shear spacing. Based on this, experiments were carried out using various thicknesses of brittle layers (specified materials) to investigate the impact of the brittle layer thickness on the R-shear spacing, and Particle Image Velocimetry (PIV) is used to analyze the distribution pattern of R-shear development at each stage. The results indicate that fractures occur in regions where the vorticity field alternates between positive and negative values, and as the evolution progresses, the maximum strain gradually converges towards the center of the deformation zone, leading to a reduction in the activity of the R-shear, while the spacing of the R-shear remains unaltered. The normalized (S/T) results indicate that the experimental value of 1.32 aligns with natural laws and is very close to the normalized value of the natural faults, which is 1.24. It can be inferred that the thickness of the seismogenic crust within the range of the Altyn Tagh Fault is 40.9–43.5 km.

Development of an Active Transportation Framework Model for Sustainable Urban Development

Active transportation, with simple mobility modes such as walking and cycling, could be pivotal in addressing multiple sustainability challenges related to socio-economic, environmental, and public health issues. This paper investigates the facilitators for active transportation and assesses its impact on health, well-being, and urban sustainability. As a result, a multidimensional conceptual framework is developed to analyze the determinants influencing individuals’ propensity to engage in active transportation and thereby lead to a sustainable, high-quality way of life. Through an extensive review of the relevant literature, key elements for active transportation, accessibility, and social inclusion are identified, and their potential impact on urban health and sustainability is investigated. Findings suggest that interrelationships between factors such as enhanced infrastructure, safety measures, and improved urban accessibility would significantly encourage active transportation usage. The proposed framework argues for a positive association between active transportation and improved health outcomes, contributing to sustainable urban environments. Furthermore, it is advocated that changing attitudes and mindsets could be achieved by urban planning and policy reforms supporting active transportation, as well as by effectively communicating the multiple benefits for individuals, the economy, and society at large. Comprehensive policy strategies, which include improvements in urban design and increased public awareness of the benefits of active transportation, could establish a paradigm shift for promoting a higher quality of life through a healthy, active, and sustainable urban lifestyle.

Causal Effects of Kidney Function and Chronic Kidney Disease on Alzheimer's Disease by Analyzing Large-Scale Genome-Wide Association Study Datasets.

Alzheimer's disease (AD) is the leading cause of dementia. Genetic components play an important role in AD and have been widely evaluated by genome-wide association studies (GWAS) and exome sequencing, and some common and rare genetic variants have been identified. In addition to genetic factors, environment factors have a role in AD. Growing evidence from observational studies linked impaired kidney function to cognitive impairment and AD; however, there are inconsistences in these findings. To determine the causal effects of impaired kidney function and chronic kidney disease (CKD) on AD. Mendelian randomization (MR) methods have been widely used to infer causal associations between exposure and outcome. Here, we conducted an MR study to investigate the causal effects of impaired kidney function and CKD on the risk of AD by analyzing large-scale GWAS datasets from FinnGen and CKD Genetics (CKDGen) Consortium. We found no significant but a suggestive effect of CKD on decreased risk of AD using inverse-variance weighted (IVW) (p = 8.46E-02) and simple mode (p = 7.60E-02) methods. We identified a statistically significant effect of the estimated glomerular filtration rate (eGFR) on increased risk of AD using IVW (p = 1.11E-02), weighted median regression (p = 5.60E-03), and weighted mode (p = 2.45E-02) methods. Together, our findings indicate that high eGFR levels may increase the risk of AD. These findings need to be verified in future studies.

Female genital prolapse and risk of psychiatric disorders: A two-sample Mendelian randomization analysis

BackgroundThere is a growing body of evidence suggests a strong link between female genital prolapse (FGP) and mental health. However, the causal relationship between FGP and psychological disorders remains unclear. ObjectivesBidirectional Mendelian Randomization (MR) analysis has been applied to investigate the potential impact of FGP on the risk of seven common psychiatric disorders. MethodsThe two-sample MR analysis was conducted using genetic instruments such as Inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode from the genome-wide association study (GWAS) summary data in European populations. In addition, the Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers (MR-PRESSO) test and leave-one-out analysis were employed to assess the sensitivity and heterogeneity. ResultsThe MR results revealed that FGP exhibited a potential marginal protective effect on bipolar disorder (BD) (odds ratio(OR) = 0.92, 95%confidence interval (95%CI: 0.85–0.99, P = 0.03) as well as schizophrenia(OR = 0.91, 95%CI:0.85–0.98, P = 0.01). Nevertheless, there was no causal correlation between genetically predicted FGP and obsessive compulsive disorder (OCD) (OR = 0.98, 95%CI:0.80–1.20, P = 0.84),depression (broad) (OR = 1.00, 95%CI:0.99–1.01, P = 0.76), major depression(OR = 0.98, 95%CI:0.94–1.03, P = 0.43), anxiety disorders (OR = 1.00, 95%CI:0.94–1.07,P = 0.97) and post-traumatic stress disorder(PTSD) (OR = 1.18, 95%CI:0.88–1.57,P = 0.27),respectively. In addition, BD was found to have a potential significant influence on FGP in the inverse MR analysis (OR = 0.83, 95%CI:0.72–0.97, P = 0.02). No significant heterogeneity or horizontal pleiotropy detected, and the results were deemed stable based on sensitivity analysis and leave-one-out test . LimitationsThere are shortcomings such as data limitations, population bias, potential pleiotropy, and stratified analysis. ConclusionsWhile there is potential causal relationship between FGP and BD or schizophrenia, it does not exhibit any correction with OCD, depression (broad), major depression, anxiety disorders and PTSD among European populations.

Causal relationship between Interleukin-27 expression levels and osteoporosis: a bidirectional mendelian randomization study

BackgroundThis study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis.MethodsFirstly, the genome-wide association study summary data of osteoporosis (finn-b-M13_OSTEOPOROSIS) and IL-27 levels (ebi-a-GCST90012017) were picked out from the Integrative Epidemiology Unit (IEU) OpenGWAS database. After filtrating instrumental variables (IVs), the bidirectional MR analysis between IL-27 levels and osteoporosis was performed by MR-Egger, Weighted median, Simple mode, Weighted mode, and Inverse variance weighted (IVW). Subsequently, the sensitivity analysis was adopted to evaluate the reliability of the MR results via the Heterogeneity, Horizontal pleiotropy test and Leave-One-Out (LOO) analysis. Finally, the enrichment analysis of genes corresponding to SNPs related to IL-27 levels derived from eQTLGen database was executed to explore in depth the biological function and regulatory mechanism of these genes on osteoporosis occurrence.ResultsThe bidirectional MR results based on IVW method revealed that IL-27 level as a risk factor was causally related to osteoporosis (P = 0.004, odds ratio (OR) = 1.123, 95% confidence interval (CI) = 1.037–1.217), whereas osteoporosis was not in significant connection with IL-27 levels (P > 0.05). In regard to the sensitivity analysis for forward MR results, there was no heterogeneity and horizontal pleiotropy, and no SNPs relevant to IL-27 levels existed severe bias, suggesting the reliability of forward MR analysis. Furthermore, a total of 74 genes corresponding to 26 SNPs of IL-27 levels were obtained and were mainly involved in immune and inflammatory pathways including MyD88-dependent toll-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway and so forth.ConclusionsThis study supported that IL-27 level as a risk factor was causally connected with osteoporosis and might regulate the disease occurrence and progression by means of immune and inflammatory mechanisms, which could provide important reference and evidence for further exploring the role of IL-27 in the development of osteoporosis.

Association of metabolites on ischemic stroke subtypes: a 2-sample Mendelian randomization study.

Metabolomics is increasingly being utilized in IS research to elucidate the intricate metabolic alterations that occur during ischemic stroke (IS). However, establishing causality in these associations remains unclear between metabolites and IS subtypes. In this study, we employ Mendelian randomization (MR) to identify specific metabolites and investigate potential causal relationships between metabolites and IS subtypes. MR analysis was conducted using genome-wide association study (GWAS) summary data. We obtained 1,091 blood metabolites and 309 metabolite ratios from the GWAS Catalog (GCST90199621-90201020), which gene sequencing data from 8,299 individuals from the Canadian Longitudinal Study. We obtained GWAS summary statistics for IS subtypes which include large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS) from the MEGASTROKE consortium that included 446,696 cases of European ancestry and 406,111 controls of European ancestry. The primary analysis utilized inverse-variance weighted (IVW) method. To validate our results, we performed supplementary analyses employing the MR-Egger, weighted median, simple mode, and weighted mode methods. Heterogeneity and pleiotropy were assessed through Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. The study assessed the possible causality of serum metabolites in the risk of IS subtypes. The discovery of significant causal links between 33 metabolites and 3 distinct IS subtypes. Metabolites show significant potential as circulating metabolic biomarkers and offer promise for clinical applications in the prevention and screening of IS subtypes. These discoveries notably advance our comprehension of the molecular processes specific to IS subtypes and create avenues for investigating targeted treatment approaches in the future.

Exploring the etiology of dilated cardiomyopathy using Mendelian randomization.

Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach. To investigate the etiology of DCM through Mendelian randomization analysis. Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods. The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference. Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.

Influence of carbon dots integrated in Pr3+ doped gahnite nanophosphor for thermal sensing, data fortification and fingerprint visualization analysis through YOLOv8x deep learning embedded model

The remarkable optical properties of carbon dots (CDs) render them highly promising as a versatile group of carbon-based nanomaterials. Integrating hydrothermally synthesized CDs into zinc aluminate doped with Pr3+ ions (ZnAl2O4:Pr3+) nanophosphors (ZAO:Pr3+ NPs) fabricated via the solution combustion (SC) technique holds great potential. The aim of synthesizing these nanocrystals (NCs) is to explore their potential uses in optical thermometry and anti-counterfeiting (AC) measures. The synthesized nanoparticles (NPs) and nanocomposites (NCs) underwent characterization using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) spectra to verify their phase, morphology, particle size, oxidation state, and chemical composition. When excited at 447 nm, the Pr3+ doped ZAO: NPs exhibited an orange-red emission band at 614 nm. A remarkable enhancement in PL intensity, by a factor of 39.02 folds, is noted upon embedding CDs into the ZAO:Pr3+ NPs (CDs@ ZAO:Pr3+). The enhanced PL intensity can be ascribed to the Förster resonance energy transfer (FRET) mechanism. Even at a temperature of 423 K, the NPs retains 95.4% of its emission intensity compared to that at room temperature, showcasing exceptional thermal stability. The 5 wt% CDs@ZAO:1Pr3+ NCs demonstrate a high colour purity (CP) of 98.3%. Moreover, these NCs hold promise for optical thermometry applications across a broad temperature range spanning from 303 to 463 K. Utilizing the exceptional ZAO:1Pr3+ NPs and 5 wt% CDs@ZAO:1Pr3+ NCs, two representative white light emitting diodes (w-LEDs) have been successfully developed, boasting satisfactory luminous efficacy and colour-rendering index (CRI). This underscores their potential for high-performance w-LED applications. Simultaneously, a highly sensitive, non-contact optical thermometer has been engineered, featuring maximum relative sensitivities of approximately 44.51×10−4K−1 and 75.48×10−4K−1 at the emission intensities corresponding to 673, 693, 712 and 735 nm, respectively. We have developed a simple brush mode technique for creating a variety of patterns using the manufactured AC security ink. The latent fingerprints (LFPs) visualized using 5 wt% CDs@ZAO:1Pr3+ NCs exhibit excellent resolution and contrast, enabling the easy identification of fingerprint characteristics from levels I-III. Employing deep learning utilizing the YOLOv8x algorithm, fluorescence images of the revealed LFPs demonstrate remarkable alignment with standard controls, suggesting a high degree of similarity. In addition, the fabricated white light emitting diode (w-LED) boasts a favorable colour rendering index (Ra=87) alongside Commission International de L′Eclairage (CIE) coordinates (0.617, 0.376). Consequently, the inclusion of 5wt% CDs@ZAO:1Pr3+NPs showcases remarkable luminescent attributes and holds promising prospects across various applications.

Vitamin D and Gestational Diabetes Mellitus in the IEU OpenGWAS Project: A Two-Sample Bidirectional Mendelian Randomization Study.

Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM. Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS). Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results. The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results. There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.

Exploring the Missing link between vitamin D and autism spectrum disorder: Scientific evidence and new perspectives

AimThis study aims to address the key question of the causal relationship between serum levels of 25-hydroxyvitamin D (vitamin D) and autism spectrum disorders (ASD). MethodsPublicly available Genome-Wide Association Study (GWAS) datasets were used to conduct the bidirectional Two-sample MR analyses using methods including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, MR-PRESSO test, Steiger filtering, and weighted mode, followed by BWMR for validation. ResultsThe MR analysis indicated that there was no causal relationship between Vitamin D as the exposure and ASD as the outcome in the positive direction of the MR analysis (IVW: OR = 0.984, 95 % CI: 0.821–1.18, P = 0.866). The subsequent BWMR validation stage yielded consistent results (OR = 0.984, 95 % CI 0.829–1.20, P = 0.994). Notably, in the reverse MR analysis with ASD as the exposure and Vitamin D as the outcome, the results suggested that the occurrence of ASD could lead to decreased Vitamin D levels (IVW: OR = 0.976, 95 % CI: 0.961–0.990, P = 0.000855), with BWMR findings in the validation stage confirming the discovery phase (OR = 0.975, 95 % CI: 0.958–0.991, P = 0.00297). For the positive MR analysis, no pleiotropy was detected in the instrumental variables. Similarly, no pleiotropy or heterogeneity was detected in the instrumental variables for the reverse MR analysis. Sensitivity analysis using the leave-one-out approach for both positive and reverse instrumental variables suggested that the MR analysis results were robust. ConclusionThrough the discovery and validation analysis process, we can confidently assert that there is no causative link between Vitamin D and ASD, and that supplementing Vitamin D is not expected to provide effective improvement for patients with ASD. Our study significantly advances a new perspective in ASD research and has a positive impact on medication guidance for patients with ASD.

Genetic insights into the association between serum cytokines and frozen shoulder risk: A bidirectional mendelian randomization study

BackgroundAlthough existing studies have indicated a connection between chronic low-grade inflammation and the onset of frozen shoulder (FS), the precise causal relationship between distinct circulating inflammatory factors and FS has yet to be thoroughly evaluated. In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between systemic cytokines and FS. MethodsA genome-wide association dataset comprising 41 serum cytokines from 8,293 individuals of Finnish descent was utilized, along with FS data from the UK Biobank included 10,104 FS cases and 451,099 controls. The primary MR method was the inverse variance weighted approach, and four additional MR techniques (MR-Egger, weighted median, simple mode, and weighted mode) were also employed to support and validate the findings. Heterogeneity and horizontal pleiotropy assessments were assessed using Cochrane’s Q and MR-Egger intercept tests. Moreover, a series of sensitivity analyses were conducted to strengthen the accuracy and credibility of these findings. ResultsBased on the IVW method, genetically predicted increasing levels of growth regulated oncogene alpha (GROa) (OR=1.08, 95 % CI 1.02–1.13, P=0.005), interferon gamma-induced protein 10 (IP-10) (OR=1.09, 95 % CI 1.02–1.17, P=0.010), regulated on activation, C–C Motif Chemokine Ligand 5 (CCL5) (OR=1.11, 95 % CI 1.03–1.20, P=0.007) were suggestively associated with an increased risk of FS. Reverse MR analysis revealed no significant causal effect of FS on the 41 systemic inflammatory factors. No heterogeneity or horizontal pleiotropy was observed in our analysis. ConclusionThis study established a causal association between 41 systemic inflammatory factors and FS, indicating that elevated levels of GROa, IP-10 and CCL5 were associated with a higher risk of FS. Further research is warranted to explore the potential of these biomarkers as early predictors and therapeutic targets for FS.

Correlation between inflammatory cytokines and the likelihood of developing multiple types of digestive system cancers: A Mendelian randomization study

ObjectiveInflammatory cytokines have been linked to digestive system cancers, yet their exact causal connection remains uncertain. Consequently, we conducted a Mendelian randomization (MR) analysis to gauge how inflammatory cytokines are linked to the risk of five prevalent digestive system cancers (DSCs). MethodsWe collected genetic variation data for 41 inflammatory cytokines from genome-wide association studies (GWAS), and the results data for five common diseases from the Finnish database. Our primary analytical approach involved employing the inverse-variance weighted, residual sum (IVW) method, complemented by the MR-Egger method, the weighted median method, simple mode analysis, and weighted mode analysis as supplementary analytical techniques. Furthermore, we conducted multiple sensitivity analyses. ResultsTumor necrosis factor-related apoptosis-inducing ligand (TRAIL), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-18 showed a negative association with the risk of hepatocellular carcinoma. Conversely, TRAIL was inversely linked to the risk of gastric cancer, while IL-16 exhibited a positive correlation with gastric cancer risk. Stem cell factor (SCF) acted as a protective factor against pancreatic cancer. For colorectal cancer, IL-7, IL-9, IL-13, and vascular endothelial growth factor (VEGF) were identified as risk factors. Notably, our results did not indicate a significant correlation between inflammatory cytokines and the risk of esophageal cancer. ConclusionOur research unveils potential connections between 41 inflammatory cytokines and the risk of five common DSCs through a MR analysis. These associations offer valuable insights that could aid in the development of diagnostic biomarkers and the identification of novel therapeutic targets for DSCs.

Rosacea and autoimmune liver diseases: a two-sample Mendelian randomization study

Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02–1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients.