Bidirectional Causal Relationship Research Articles

The Impact of Financial Development, Foreign Direct Investment, and Trade Openness on Carbon Dioxide Emissions in Jordan: An ARDL and VECM Analysis Approach

Jordan has made substantial strides in enhancing its economy by focusing on economic growth stimulants, which include financial development, foreign direct investment (FDI), and trade openness. However, these economic activities often lead to significant environmental risks. Despite their relevance, the existing literature has rarely examined the influence of these dynamics on environmental quality in the Middle East, particularly in Jordan. This study aims to investigate the influence of financial development, FDI, and trade openness on carbon dioxide (CO2) emissions in Jordan. To achieve this, the study employs the Autoregressive Distributed Lag (ARDL) technique and the Vector Error Correction Model (VECM) Granger causality approach, utilizing data sourced from the World Bank for the period from 1990 to 2022. The findings indicate that financial development, FDI, and trade openness positively impact CO2 emissions, thereby increasing environmental risks in both the short and long term. Additionally, there exists a bidirectional causal relationship between financial development and both FDI and trade openness, as well as between FDI and trade openness. It is imperative for Jordan to design strategies that balance economic growth with sustainable environmental practices.

The causal relationship between trace element status and upper gastrointestinal ulcers: a Mendelian randomization study

BackgroundThis study aimed to investigate the bidirectional causal relationships between trace elements (such as zinc, magnesium, phosphate, and folate) and upper gastrointestinal ulcers (including gastric and duodenal ulcers). We utilized a two-sample Mendelian randomization (MR) analysis to achieve this.MethodsWe conducted a two-sample MR analysis using summary-level data from genome-wide association studies (GWAS) obtained from public genomics repositories. We utilized a range of MR methods, including inverse-variance weighted (IVW), MR-Egger, and weighted median methods, and conducted a meta-analysis to synthesize results across different datasets. To ensure the robustness of our findings, we performed extensive sensitivity analyses, including pleiotropy assessment, heterogeneity tests, and leave-one-out analysis.ResultsOur findings are significant, indicating a positive causal relationship between increased zinc levels and the risk of gastric ulcers. Moreover, magnesium and folate appear to offer potential protective effects against gastroduodenal ulcers (p < 0.05). The meta-analysis further supports the causal relationship between zinc and gastric ulcers (p < 0.05), confirming zinc’s significant causal impact on this condition.ConclusionThe study confirms a positive causal relationship between zinc and gastric ulcers and highlights the complexity of how trace elements regulate the progression of upper gastrointestinal ulcers. These results provide a scientific basis for dietary recommendations regarding trace element intake in clinical and public health practices. They also offer new insights into effective prevention and treatment strategies for gastric and duodenal ulcers.

Investor attention and market activity: evidence from green cryptocurrencies

Purpose This paper aims to investigate the relationship between investor attention and market activity (return, volatility and volume) using a sample of 14 clean energy cryptocurrencies (hereafter green cryptocurrency), namely, Chia, Cardano, Stellar, Tron, Ripple, Nano, IOTA, EOS, Bitcoin Green, Alogrand, Hedara, Polkadot, FLOW and Tezos. Design/methodology/approach This paper use 26040 crypto-day observations and a range of econometric techniques, including Dynamic Granger causality, Panel vector autoregression (VAR), Impulse response function and the decomposition of forecast error variance. Findings Based on 26040 crypto-day observations, this paper finds a bidirectional Granger causal relationship between investor attention and all measures of market activity, namely, return, absolute volatility, squared volatility and volume. The panel VAR and impulse response function demonstrate that market activity in the green crypto ecosystem, especially volatility and volume, is considerably responsive to changes in investor attention proxied by Google search volume (hereafter Google search volume (GSV)). The findings also demonstrate a significant asymmetric effect of return and volume on investor attention since past negative shocks “or bad news” in return and volume are more likely to grab the investor’s attention. All in all, our study emphasizes the crucial role of investor attention in the green crypto ecosystem. Originality/value (i) The research is the first to shed light on investor attention in the green cryptocurrency market. (ii) The paper uses a wide range of green cryptocurrencies to offer a comprehensive picture of the green cryptocurrency ecosystem. (iii) This paper is the first to use the panel Granger causality to investigate investor attention in the cryptocurrency market which provides several advantages over the conventional Granger causality approach. (iv) This paper is the first to provide novel empirical evidence on the prevalent influence of investor attention in the green crypto market.

Causality of immune cells and endometriosis: a bidirectional mendelian randomization study

BackgroundEndometriosis, a prevalent chronic condition, afflicts approximately 10% of women in their reproductive years. Emerging evidence implicates immune cells in the pathogenesis of endometriosis, particularly in angiogenesis, tissue proliferation, and lesion invasion. This investigation employs two-sample Mendelian Randomization (MR) to dissect the bidirectional causal relationships between immune cell profiles and endometriosis.MethodsWe leveraged publicly available genome-wide association study (GWAS) data to elucidate the causal interplay between immune cell traits and endometriosis. Utilizing GWAS summary statistics ranging from accession numbers GCST90001391 to GCST90002121 and endometriosis data from the FinnGen study GWAS (8,288 endometriosis cases and 68,969 controls), we adopted stringent criteria for instrumental variable selection. We applied MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods to derive causal estimates. To address potential heterogeneity and pleiotropy, Cochran’s Q test, MR-Egger intercept, and leave-one-out analyses were executed. Reverse-direction MR and bidirectional MR analyses evaluated potential reciprocal causation and the influence of endometriosis on immune cell composition.ResultsOur analysis identified five immune phenotypes inversely associated with endometriosis risk. These phenotypes comprise: a percentage of CD11c + HLA-DR + + monocytes, CD25 expression on CD39 + CD4 + T cells, elevated CD25 on CD45RA + CD4 + non-regulatory T cells, HLA-DR intensity on HLA-DR + CD8 bright (CD8br) T cells, and the proportion of naïve double-negative (CD4 − CD8− %DN) T cells. In contrast, eleven phenotypes were positively correlated with endometriosis risk, including: CD127 expression on T cells, the proportion of CD24 + CD27 + B cells within lymphocytes, CD25 expression on CD28 + CD4 + T cells, CD28 expression on CD39 + activated regulatory T cells (activated Tregs), the frequency of bright CD33 HLA-DR + CD14 − cells within the CD33br HLA-DR + compartment, CD45 expression on lymphocytes and natural killer (NK) cells, activation status of central memory CD8 bright (CM CD8br) T cells, CX3CR1 expression on monocytes, and the percentage of HLA-DR + NK cells within the NK cell subset. Sensitivity assessments that excluded significant heterogeneity and pleiotropy confirmed the stability of these associations, thereby reinforcing the validity of our findings.ConclusionThis study provides novel evidence of the potential causal impact of specific immune cells on the risk of developing endometriosis. These findings enhance our understanding of endometriosis pathophysiology and may inform innovative approaches for its diagnosis and management. While our findings provide novel insights, limitations such as potential horizontal pleiotropy and reliance on European ancestry data should be considered. Future research should expand to diverse populations and incorporate individual-level data to refine these findings.

Linking Human Development Index, Urbanization, Economic Growth and the Ecological Footprint: The Case of MINT Countries

The main purpose of this study is to investigate the relationship between human development index, urbanization, economic growth and ecological footprint in MINT countries (Mexico, Indonesia, Nigeria and Turkiye) for the years 2003-2022. First of all, the cointegration relationship between human development index, urbanization, economic growth and ecological footprint was examined with Gengenbach, Urbain and Westerlund (2016) panel cointegration. As a result of the cointegration analysis, it was concluded that the variables were cointegrated. The long-term relationship was estimated by the DOLSMG method. According to the DOLSMG estimator, it was determined that a 1% increase in the human development index in MINT countries reduced the ecological footprint by 1.89%, a 1% increase in urbanization increased the ecological footprint by 0.22%, and a 1% increase in economic growth increased the ecological footprint insignificantly. Secondly, the relationship between human development index, urbanization, economic growth and ecological footprint was examined with Dumitrescu and Hurlin (2012) panel causality analysis. According to the findings, there is a bidirectional causality relationship between ecological footprint and urbanization in MINT countries. Additionally, the findings of the study show that there is a unidirectional causality relationship from ecological footprint to human development index and a unidirectional causality relationship from economic growth to ecological footprint.

Bidirectional causal relationship between glucose-lipid metabolism, obesity indicators, and myocardial infarction: a bidirectional Mendelian randomization analysis study

Objective: To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis. Methods: Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran's Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results: Higher BMI (OR=1.070, 95%CI: 1.041-1.100), waist-to-hip ratio (OR=1.366, 95%CI: 1.113-1.677), LDL-C (OR=1.638, 95%CI: 1.488-1.803), triglycerides (OR=1.445, 95%CI: 1.300-1.606), waist circumference (OR=1.841, 95%CI: 1.650-2.055), hip circumference (OR=1.247, 95%CI: 1.132-1.372), body fat percentage (OR=1.795, 95%CI: 1.568-2.055), whole-body fat mass (OR=1.519, 95%CI: 1.381-1.670), trunk fat percentage (OR=1.538, 95%CI: 1.374-1.723), and trunk fat mass (OR=1.421, 95%CI: 1.294-1.561), as well as lower HDL-C (OR=0.799, 95%CI: 0.729-0.875), have causal effects on myocardial infarction (all P<0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio (OR=1.457, 95%CI: 1.132-1.877), fasting glucose (OR=1.191, 95%CI: 1.024-1.383), glycated hemoglobin (OR=1.129, 95%CI: 1.034-1.233), LDL-C (OR=1.592, 95%CI: 1.314-1.929), triglycerides (OR=1.410, 95%CI: 1.279-1.553), waist circumference (OR=1.922, 95%CI: 1.448-2.551), body fat percentage (OR=1.421, 95%CI: 1.072-1.884), and whole-body fat mass (OR=1.295, 95%CI: 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C (OR=0.809, 95%CI: 0.729-0.897) remained negatively associated. Conclusions: Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.

Investigating the genetic causal relationship between breast cancer and endometrial cancer: A two-sample Mendelian randomization study.

Observational studies have consistently shown a correlation between breast cancer (BC) and endometrial cancer (EC). Despite these findings, the causal relationship between these cancers has not been clearly defined. This research employed a bidirectional two-sample Mendelian randomization to explore the genetic causality between BC and EC. Genetic instruments for BC were derived from the Breast Cancer Association Consortium genome-wide association studies summary statistics, while for EC, data were sourced from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. The primary analytical method was inverse-variance weighted. Additional analyses, such as MR-Egger and weighted median, were conducted to validate the robustness of our findings from multiple perspectives. The MR-Egger intercept test was conducted to examine potential pleiotropy, whereas Cochrane Q test was implemented to assess heterogeneity. A leave-one-out analysis was conducted to assess the sensitivity of the observed association. Our analysis identified a bidirectional genetic causal relationship between estrogen receptor-positive breast cancer (ER+BC) and EC. Inverse-variance weighted analysis indicated an odds ratio of 1.0686 (95% confidence interval: 1.0029-1.1386, P = .0403) from ER+BC to EC and an odds ratio of 1.0692 (95% confidence interval: 1.0183-1.1225, P = .0071) from EC to ER+BC. No significant horizontal pleiotropy was detected. This study confirms a bidirectional genetic link between ER+BC and EC, suggesting shared genetic etiologies and possibly linked pathophysiological pathways. Understanding the genetic interplay between ER+BC and EC can enhance strategies for the precise prevention and screening of these prevalent cancers, potentially leading to improved clinical outcomes and management of secondary primary malignancies.

Causal Relationship Between Post-Traumatic Stress Disorder and Immune Cell Traits: A Mendelian Randomization Study.

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that occurs after exposure to catastrophic-level experiences. Although alterations in immune function have been identified in individuals with PTSD, the causal relationship between the two remains unclear. To investigate the causal relationship between PTSD and immune function, we conducted the forward and backward two-sample Mendelian randomization (MR) analyses, based on summary-level genome-wide association studies (GWAS) data on PTSD and immune cell traits. For the forward MR analysis, PTSD was found to reduce the levels of CD62L- dendritic cell (DC) (beta=-0.254, FDR=0.01), CD86+ myeloid DC (beta=-0.238, FDR=0.014), CD62L- myeloid DC (beta=-0.26, FDR=0.01), CD62L- CD86+ myeloid DC absolute count (beta=-0.264, FDR=0.024), and CD62L- CD86+ myeloid DC (beta=-0.328, FDR=0.002). In contrast, PTSD was observed to increase the level of CD28- CD8dim T-cell absolute count (beta=0.27, FDR=0.029). For the backward MR analysis, the odds ratio (OR) for CD33 on CD33dim HLA DR+ CD11b- in relation to PTSD risk was found to be 1.045 (95% CI=1.021-1.069, FDR=0.008). The OR for FSC-A on HLA DR+ CD8br was 1.048 (95% CI=1.018-1.079, FDR=0.039) and for CCR2 on CD14- CD16+ monocyte was 1.059 (95% CI=1.027-1.092, FDR=0.008). No significant pleiotropy was detected in both forward and backward MR analyses. The bidirectional MR study shed light on the intricate interplay between immune function and PTSD. The identification of a bidirectional causal relationship between T cells and PTSD opens new avenues for considering innovative approaches to the prevention and early intervention of PTSD.

Level Analysıs of the Relatıonshıp Between Inflatıon, Exchange Rate, Cbrt and Fed Interest Rates of Turkısh Foreıgn Trade

Foreign trade has become one of the important elements of the financial structure of countries. Money transfer mechanisms have the power to determine the direction of trade in the world. In the study; Türkiye's exports acording to the country groups were used. In the period 2013:1-2023:11; Panel cointegration, Autoregressive Distributed Lag (ARDL) and Granger causality analyses were used to determine the relationship levels between the Central Bank of the Republic of Türkiye (CBRT), Federal Reserve System (FED) interest rates, Wholesale Price Index (WPI), Consumer Price Index (CPI) and Türkiye's foreign trade. has been used. As a result of the study; Findings have been obtained that Turkish exports are not affected by the CBRT interest rate decisions and WPI in the short or long term. While the increase in FED interest rates causes a decrease in all of Türkiye's exports in the long term, it reduces exports to the Turkic Republics, OECD, EFTA, BSEC, CIS, OIC and D8G in the short term. It has been concluded that while there is a unidirectional causality relationship between the CBRT and FED interest rates, WPI and CPI and Türkiye's exports, there is a bidirectional causality relationship between the exchange rate and Türkiye's exports.

Metabolite, immunocyte phenotype, and lymphoma: a Mendelian randomization study.

Recent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear. To elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis. Applying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype. This study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma. In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a mediator of the negative association of X-18922(unknown metabolite) levels with diffuse large B-cell lymphoma, with a mediation proportion of -8.940% (95% CI=-0.063-(-17.800) %, P=4.84 × 10-2). CD25 on IgD- CD24- B cell was the mediator of the positive association between X-24531(unknown metabolite) levels and diffuse large B-cell lymphoma, with a mediation proportion of 13.200% (95% CI=-0.156-26.200%, P=4.73 × 10-2). In the present study, we identified a causal relationship between metabolites and lymphoma, in which immunocyte phenotypes as mediators are involved in only a minor part. The mediators by which most metabolites affect the risk of lymphoma development remain unclear and require further exploration in the future.

Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.

Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint. We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p-value, OR (Odds Ratio), and 95% confidence interval (95% CI). From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; p = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; p = 0.002), respectively. No significant causal relationship was found between aspirin and MD (p > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, p = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, p = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, p = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings. This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.

A Dynamic Analysis of Sustainable Economic Growth and FDI Inflow in Saudi Arabia Using ARDL Approach and VECM Technique

This study investigates the relationship between sustainable economic growth and foreign direct investment (FDI) in Saudi Arabia from 1980 to 2023. The ARDL approach and VECM technique are employed to analyze the short-run and long-run dynamics. The short-run results show mixed effects. Sustainable economic growth has a positive impact on current and one-period lagged FDI but a negative impact on the two periods lagged. Trade openness and infrastructure negatively affect FDI in the short run. Interestingly, oil rents and real economic growth also have negative short-run impacts on FDI, but these effects become positive with a longer lag. Long-run analysis reveals a negative relationship between trade openness, infrastructure, and oil rents with FDI, suggesting a potential crowding-out effect. Trade openness has a positive long-run impact on most variables, including sustainable growth, FDI, real growth, and CO2 emissions. Oil rents also have a positive long-run impact on these variables. This study finds six bidirectional causal relationships in the short run, primarily between trade openness, infrastructure, oil rents, and FDI. Unidirectional causality runs from oil rents, trade openness, exchange rate, sustainable growth, and real growth to FDI and infrastructure. Additionally, CO2 emissions cause FDI, and trade openness causes sustainable growth. While sustainable economic growth benefits FDI in the long run, short-term policies regarding trade openness and infrastructure require reevaluation. Oil revenue and real economic growth may initially deter FDI, but this reverses in the long term. To attract sustainable FDI, policymakers should focus on long-term economic growth strategies and consider reforms in trade and infrastructure policies. A comprehensive FDI strategy that moves beyond oil dependence and leverages trade openness is crucial to long-term economic diversification.

Investigating the determinants of marine environmental degradation in Africa: What roles can economy, population, capture and energy play?

This study firstly examines the quality of marine eco-environment in Africa using Tapio decoupling model, and analyzes the sustainability level of the development of “population agglomeration - marine environment - economic growth”. Secondly, a series of econometric tools, such as ARDL, FMOLS, AMG model and DH panel causality test, are used to investigate the long- and short-term impacts of economic growth, population agglomeration, marine capture and energy consumption on the African marine eco-environment, and to analyze the differences between the sub-regions in Africa. The results indicate that: Adebayo and Kirikkaleli (2021) (Adebayo and Kirikkaleli, 2021) the decoupling state of “population-environment” has shifted from expansive negative decoupling to more optimized strong decoupling, and “economy-environment” has gradually changed from strong negative decoupling and expansive negative decoupling to strong decoupling. Ali et al. (2017) (Ali et al., 2017) There existed a bi-directional causal relationship between the degree of marine environment degradation and economic growth, population agglomeration, marine capture and energy consumption. Al-Mulali and Sab (2012) (Al-Mulali and Sab, 2012) In the short term, the economic EKC hypothesis does not hold in North and West Africa, while Central, East and Southern Africa are consistent with the EKC hypothesis. In the long term, the EKC hypothesis is valid in Central, East and Southern Africa, while is not valid in North and West Africa. Overall, reducing population agglomeration levels, marine fishing and energy consumption might mitigate marine environmental degradation in Africa.

Bidirectional association between perioperative skeletal muscle and subcutaneous fat in colorectal cancer patients and their prognostic significance.

Low skeletal muscle mass and high adipose tissue coexist across the body weight spectrum and independently predict the survival ratio of colorectal cancer (CRC) patients. This combination may lead to a mutually exacerbating vicious cycle. Tumor-associated metabolic conditions primarily affect subcutaneous adipose tissue, but the nature and direction of its relationship with skeletal muscle are unclear. This study aims to examine the bidirectional causal relationship between skeletal muscle index (SMI) and subcutaneous fat index (SFI) during the perioperative period in CRC patients; as well as to validate the association between perioperative SMI, SFI, and CRC prognosis. This population-based retrospective cohort study included patients with stage I-III colorectal cancer who underwent radical resection at the Third Affiliated Hospital of Kunming Medical University between September 2012 and February 2019. Based on inclusion and exclusion criteria, 1,448 patients were analyzed. Preoperative (P1), 2 months postoperative (P2), and 5 months postoperative (P3) CT scans were collected to evaluate the skeletal muscle index (SMI; muscle area at the third lumbar vertebra divided by height squared) and subcutaneous fat index (SFI; subcutaneous fat area at the third lumbar vertebra divided by height squared). A random intercept cross-lagged panel model (RI-CLPM) was used to examine the intra-individual relationship between SMI and SFI, and Cox regression was employed to assess the association between SMI, SFI, recurrence-free survival (RFS), and overall survival (OS). The median age at diagnosis was 59.00 years (IQR: 51.00-66.00), and 587 patients (40.54%) were female. RI-CLPM analysis revealed a negative correlation between SFI and subsequent SMI at the individual level: P1-P2 (β = -0.372, p = 0.038) and P2-P3 (β = -0.363, p = 0.001). SMI and SFI showed a negative correlation during P1-P2 (β = -0.363, p = 0.001) but a positive correlation during P2-P3 (β = 0.357, p = 0.006). No significant correlation was found between the random intercepts of SFI and SMI at the between-person level (r = 0.157, p = 0.603). The Cox proportional hazards multivariate regression model identified that patients with elevated SFI had poorer recurrence-free survival (HR, 1.24; 95% CI: 1.00-1.55). Compared to patients with normal preoperative SMI and SFI, those with low SMI or high SFI had poorer recurrence-free survival (HR, 1.26; 95% CI: 1.03-1.55) and overall survival (HR, 1.39; 95% CI: 1.04-1.87). However, no significant association between SMI and SFI and the prognosis of colorectal cancer patients was observed postoperatively. In CRC patients, preoperative muscle loss leads to postoperative fat accumulation, exacerbating muscle loss in a feedback loop. Elevated preoperative SFI predicts poorer survival outcomes. Monitoring SMI and SFI is crucial as prognostic indicators, despite non-significant postoperative associations. Further research is needed to improve patient outcomes.

Causal Associations of Sleep Apnea With Alzheimer Disease and Cardiovascular Disease: A Bidirectional Mendelian Randomization Analysis.

Sleep apnea (SA) has been linked to an increased risk of dementia in numerous observational studies; whether this is driven by neurodegenerative, vascular, or other mechanisms is not clear. We sought to examine the bidirectional causal relationships between SA, Alzheimer disease (AD), coronary artery disease (CAD), and ischemic stroke using Mendelian randomization. Using summary statistics from 4 recent, large genome-wide association studies of SA (n=523 366), AD (n=94 437), CAD (n=1 165 690), and stroke (n=1 308 460), we conducted bidirectional 2-sample Mendelian randomization analyses. Our primary analytic method was fixed-effects inverse variance-weighted (IVW) Mendelian randomization; diagnostics tests and sensitivity analyses were conducted to verify the robustness of the results. We identified a significant causal effect of SA on the risk of CAD (odds ratio [ORIVW]=1.35 per log-odds increase in SA liability [95% CI=1.25-1.47]) and stroke (ORIVW=1.13 [95% CI=1.01-1.25]). These associations were somewhat attenuated after excluding single-nucleotide polymorphisms associated with body mass index (ORIVW=1.26 [95% CI=1.15-1.39] for CAD risk; ORIVW=1.08 [95% CI=0.96-1.22] for stroke risk). SA was not causally associated with a higher risk of AD (ORIVW=1.14 [95% CI=0.91-1.43]). We did not find causal effects of AD, CAD, or stroke on risk of SA. These results suggest that SA increased the risk of CAD, and the identified causal association with stroke risk may be confounded by body mass index. Moreover, no causal effect of SA on AD risk was found. Future studies are warranted to investigate cardiovascular pathways between sleep disorders, including SA, and dementia.

Causal association between hyperthyroidism and risk of gastroesophageal reflux or esophageal cancer: a bidirectional Mendelian randomization investigation.

Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer. To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results. When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer. Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.

Analysis of Genetic Risk Factors Associated with Charcot Foot Based on the FinnGen Study R9 Data: A Wide-angle Mendelian Randomization Study.

Charcot foot or Charcot neuropathic joint disease (CN) is a rare and complex foot disease with unknown pathogenesis, hindering early identification and intervention. The study aimed to clarify the causal association between all predominant risk factors and CN. Two-sample Mendelian Randomization (MR), Multivariate MR, and Bidirectional MR analyses investigated the causal association between 36 modifiable risk factors and CN. The causal relationship between CN and Inflammatory cytokine and immune cells was also analyzed. Genetic factors associated with obesity and genetic susceptibility to various autoimmune diseases and non-cancerous thyroid diseases increased the risk of CN (P < .05), genetically associated high basal metabolic rate and high total cholesterol decreased the risk of CN (P < .05). In addition, we found a bi-directional causal relationship between CN and diabetes. In further immune cell analysis, we found 8 CN related immune cells, and in inflammatory cytokine analysis, we found 2 CN related inflammatory cytokines. This comprehensive MR Study supports the causal role of Obesity-related factors, diabetes, autoimmune-related factors, and smoking in the development and progression of CN. This study identifies a potential cause of CN that has not been identified in previous studies and provides a new direction for further research.

Empowering energy access: Exploring financial inclusion's impact on energy poverty in the fragile five economies

Energy poverty is a major issue that deepens economic challenges, especially in the five fragile states of Turkey, Brazil, South Africa, India, and Indonesia. The objective of this study is to examine the impact of financial inclusion on energy poverty, as removing financial barriers to energy access and utilisation is critical for sustainable development. The study hypothesizes that financial inclusion plays a decisive role in alleviating energy poverty. The study analyses the second generation panel methods such as AMG, Driscool-Kraay, and FMOLS using annual data from 2000 to 2021 and examines the causal relationships between variables using Dumitrescu-Hurlin panel causality test. The findings reveal that financial inclusion, low carbon technology trade, energy efficiency, economic growth, and human capital play a central role in alleviating energy poverty in these economies. On the other hand, a unidirectional causal relationship was found between financial inclusion and low carbon technology trade, human capital, energy efficiency, and energy poverty. In contrast, a bidirectional causal relationship was observed between economic growth and energy poverty. These findings provide important insights for policymakers and stakeholders; understanding the complex dynamics between financial inclusion and energy poverty can help design targeted strategies to increase energy access and promote inclusive economic development in fragile economies.

Causal relationship between Brugada syndrome and electrocardiogram traits: A bidirectional Mendelian randomization study

IntroductionObservational studies have suggested associations between Brugada syndrome (BrS) and electrocardiograms traits. Nonetheless, the causal relationships remains uncertain in observational studies. This study aims to investigate the causal relationships between BrS phenotypic risk and electrocardiogram traits using Mendelian randomization (MR) analysis and colocalization analysis. MethodsMR analysis was performed to investigate the causal relationships between BrS phenotype risk and electrocardiogram traits (P wave duration, PR interval, QRS wave duration, ST segment duration, T wave duration, QT interval, heart rate (HR) and heart rate variability). The genetic instruments for BrS (number of cases = 12,821) were obtained from the latest GWAS. GWAS summary data of electrocardiogram traits were obtained from the MRC-IEU and GWAS catalog databases. The causal relationships were obtained through MR methods, and sensitivity analyses (e.g. Cochran's Q test, MR-PRESSO). Furthermore, the causal relationships were evaluated whether they were driven by one linkage disequilibrium using colocalization analysis. ResultsWe found that there are positive causal relationships between BrS phenotypic risk and P wave duration, PR interval, QRS wave duration and QT interval, respectively (IVWP: β = 1.238, 95 % CI = 0.857–1.619, P<0.001; IVWPR: β = 2.199, 95 % CI = 1.358–3.039, P<0.001; IVWQRS: β = 0.157, 95 % CI = 0.115–0.198, P<0.001; IVWQT: β = 0.593, 95 % CI = 0.391–0.796, P<0.001), and there is a negative causal relationship between BrS phenotypic risk and heart rate (IVWHR: β = −0.023, 95 % CI = −0.03 ∼ −0.015, P<0.001). Additionally, there are bidirectional causal relationships between BrS phenotypic risk and P wave duration and PR interval, respectively (IVWP: OR = 1.217, 95 % CI = 1.118–1.325, P<0.001; IVWPR: OR = 1.02, 95 % CI = 1.008–1.032, P = 0.001). Furthermore, colocalization analysis identified that the causal relationships between BrS phenotype risk and P wave duration, PR interval and QRS wave duration were driven by rs6790396, rs6801957 and rs6801957, respectively. ConclusionsBidirectional causal relationships were identified between BrS phenotypic risk and P wave duration and PR interval, respectively. There were positive causal relationships between BrS phenotypic risk and QRS wave duration and QT interval, respectively, and there is a negative causal relationship between BrS phenotypic risk and heart rate.

A causal association between esophageal cancer and the oral microbiome: a Mendelian randomization study based on an Asian population.

Previous studies have suggested a crosstalk between the oral microbiome and esophageal cancer (EC), but the exact relationship is unclear. This study aimed to investigate the causal relationship between changes in the oral microbiome and EC by Mendelian randomization (MR). In the study, bidirectional MR analyses were conducted using genome-wide association study data from the oral microbiomes from the 4D-SZ cohort and EC data from the BioBank Japan cohort. Multiple sensitivity tests, including Cochrane's Q statistic, MR-Egger intercept, and MR-PRESSO, were used to assess and validate the relative stability of the resulting data at various levels. Among the 3,117 samples studied, 73 oral microbiomes were found to be statistically causally associated with EC, 38 of which were considered protective factors. According to species analyses, positive results were concentrated in three phyla: Firmicutes (29 species), Patescibacteria (18 species), and Actinobacteria (9 species). It was also determined that Parvimonas micra, Aggregatibacter, and Clostridia had a negative causal relationship, implying that EC caused a decrease in the counts. Following p-value correction, periodonticum_C, unclassified_mgs_3234, and unclassified_mgs_45 were identified as having a strong evidence-grade causal relationship with EC. There was no strong evidence in the results of the inverse MR analyses of EC to the oral microbiome. The sensitivity analysis confirmed the robustness of the findings. This study discovered a bidirectional causal relationship between the oral microbiome and EC, which may provide new insights into the future use of the microbiome for early screening and probiotic therapy.