Instrumental Variable Research Articles

Importance of repayment capacity in the quantitative rationing of agricultural credit in Benin

PurposeThis paper analyzes the effect of repayment capacity on the quantitative rationing of credit to agricultural credit applicants.Design/methodology/approachThe empirical analysis of credit supply involved 595 applicants for agricultural credit. The instrumental variable (IV) approach of probit and tobit was used to identify credit rationing factors.FindingsAll things being equal, a 1% increase in repayment capacity increases the amount received by 25% for large applicants, and 47% for small applicants. Other variables related to equity, participation rate, crops produced, reputation, age, activity stability and proximity influence the credit supply.Research limitations/implicationsThe results of this study provide a theoretical basis for comparing small and large agricultural credit applicants, which is essential for better decision-making by financial institutions and the government. This article recommends that all applicants should have a good reputation and keep their business income and expenditure book up-to-date, that small applicants should invest in their business and improve their financial education and that large applicants should accumulate wealth and invest in perennial crops. As a limitation of this study, it would be possible to extend the data to other institutions using panel data.Originality/valueThe originality of this study lies in its consideration of the endogeneity problem between repayment capacity and credit rationing and, in a comparative analysis of small and large credit applicants. The results of this analysis will be used to adjust agricultural credit granting policies.

Digital economy, international openness, and innovation capability: empirical evidence from Urban China

Abstract Using urban panel data from 2011 to 2019 in China, this study employs various econometric models to analyze the impact and mechanism of digital economy (DE) development on urban innovation capabilities. The empirical results show that DE development significantly bolsters urban innovation in China, a finding that remains consistent even after conducting rigorous robustness tests, such as using historical data as instrumental variables. Importantly, an analysis using the spatial Durbin model reveals a positive spatial spillover effect—DE development in one city enhancing innovation capabilities in neighboring cities. This effect not only diminishes the regional innovation gap but also stimulates regional coordinated innovation. The study also illustrates that a city’s degree of international openness enhances the positive impact of DE development on urban innovation capabilities. This highlights that promoting regional openness is an important mechanism to facilitate the beneficial effect of DE development on urban innovation capabilities. Providing both theoretical foundation and empirical evidence for the impact of DE development, this paper contributes valuable insights into promoting innovation-driven development via digital ecosystem empowerment, formulating differentiated DE strategies, and maximizing the spatial spillover effects of the DE.

CD8 + T cells may mediate the effect of gut microbiota on psoriasis: evidence from two-step mendelian randomization and bayesian weighting.

Emerging research indicates that gut microbiota and the associated immune responses are crucial in the development of chronic inflammatory skin diseases. This investigation employs Mendelian Randomization (MR) and Bayesian weighting to elucidate the causal links between gut microbiota, immune cells, and psoriasis, with a specific emphasis on CD8 + T cells. We leveraged summary statistics from genome-wide association studies (GWAS) related to gut microbiota, immune cells, and psoriasis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs) to evaluate causal relationships through various MR methods, such as inverse variance weighted (IVW), MR Egger, weighted median, and simple mode. Additionally, Bayesian weighting was used to validate results and account for potential pleiotropy. The IVW analysis revealed significant associations between certain gut microbiota and psoriasis, notably identifying a protective link between Escherichia coli and psoriasis. Further MR analysis demonstrated that Escherichia coli had a causal relationship with CD8 + T cells. Increased levels of CD8 + T cells were associated with a higher risk of psoriasis. BWMR analysis confirmed these findings, showing that CD8 + T cells mediated 10.09% of the protective effect of Escherichia coli on psoriasis. This study underscores the significant role of Escherichia coli and CD8 + T cells in psoriasis, suggesting both protective and exacerbating effects. Understanding these microbiota-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk

BackgroundThe liver‒brain axis is critical in neurodegenerative diseases (NDs), with lipid metabolism influencing neuroinflammation and microglial function. A systematic investigation of the genetic relationship between lipid metabolism abnormalities and ND, namely, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), is lacking. To assess potential causal links between ND and six lipid parameters, two-sample Mendelian randomization (MR) was used.MethodsLarge-scale European ancestry GWAS data for lipid parameters and ND (AD, ALS, PD, and MS) were used. Genetic variants demonstrating significant correlations (P < 5 × 10−8) with lipid metabolism parameters were identified and employed as instrumental variables (IVs) after proper validation. The research incorporated UK Biobank genomic data to examine associations between genetic variants and lipid metabolism parameters. The analysis included primary MR, sensitivity analyses, and multivariable MR, which considered potential mediators.ResultsMR via the inverse-variance weighted method revealed causal effects of cholesterol (CHOL, OR = 1.10, 95% CI: 1.03–1.18, P = 4.23 × 10⁻3) and low-density lipoprotein cholesterol (LDLC, OR = 1.10, 95% CI: 1.03–1.17, P = 3.28 × 10⁻3) on the risk of ALS, which were validated across multiple methods. Potential correlations were observed between ApoB and ALS and inversely correlated with AD, whereas no significant associations were found for PD or MS. CHOL and LDLC associations with ALS demonstrated no significant heterogeneity or pleiotropy, supporting their reliability.ConclusionsHigher CHOL and LDLC levels were associated with increased ALS risk, suggesting a potential causal link, and supporting the liver‒brain axis hypothesis in ND. Current genetic evidence does not support a significant role for lipid metabolism in PD and MS etiology, suggesting the relationship between lipid metabolism and other NDs may be more complex and warrants further investigation.

Causal associations between socioeconomic status and prostate cancer using two-sample Mendelian randomization study

Prostate cancer (PCa) is a common form of malignancy among men. The associations between socioeconomic status (SES) indicators and PCa risks remain incompletely elucidated. Through two-sample Mendelian randomization (MR), this research seeks to assess the causal links between 4 genetically predicted SES indicators—average total household income before tax, the Townsend deprivation index at recruitment, unemployed status and college or university degree in the household—and PCa. Genetic variants were extracted from publicly available genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger to estimate the causal effect, with sensitivity analyses such as Cochran’s Q tests, MR-Egger, MR-PRESSO and leave-one-out performed to detect potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between unemployment and prostate cancer (OR: 3.07, 95%CI:1.12–8.42, P = 0.03). No causal associations were identified between other SES components and prostate cancer. The MR-PRESSO suggested 2 outliers in the association between college or university degree in household and prostate cancer, which rendered the association significant after outliers were removed. The heterogeneity and pleiotropy are unlikely to affect our causal estimate. Our results indicated that unemployment poses a potential risk factor for the incidence of PCa. The findings highlight the necessity for further exploration into the underlying etiology of PCa.

Multivariate proteome-wide association study to identify causal proteins for Alzheimer disease.

Alzheimer disease (AD) is a complex and progressive neurodegenerative disorder that accounts for the majority of individuals with dementia. Here, we aim to identify causal plasma proteins for AD, shedding light on the etiology of AD. We utilized the latest large-scale plasma proteomic data from the UK Biobank Pharma Proteomics Project (UKB-PPP) and AD genome-wide association study (GWAS) summary data from the International Genomics of Alzheimer's Project (IGAP). Via a robust univariate instrumental variable (IV) regression method, we identified causal proteins through cis-protein quantitative trait loci (pQTLs) and (both cis- and trans-)pQTLs. To further reduce potential false positives due to high linkage disequilibrium (LD) of some pQTLs and high correlations among some proteins, we developed a robust multivariate IV regression method, called two-stage constrained maximum likelihood (MV-2ScML), to distinguish direct and confounding/mediating effects of proteins; some key features of the method include its robustness to invalid IVs and applicability to GWAS summary data. Our work highlights some differences between using cis-pQTLs and trans-pQTLs and critical values of multivariate analysis for fine-mapping causal proteins, providing insights into plasma protein pathways to AD.

The influence of spousal care on the health of middle-aged and older adult caregivers in China—empirical analysis based on CHARLS data

ObjectivesWith the decrease of the number of children and the increase of population mobility, child care presents a phenomenon of “double shortage” of human and time resources, and spousal care is becoming an important care source for middle-aged and older adult people in China. However, less studies have taken middle-aged and older adult couples as research subject to explore the health effects of spousal care in the process of aging. This paper attempts to explore the effects of caregiving on the health of caregivers from the perspective of spousal care.MethodsUsing China Health and Retirement Longitudinal Study (CHARLS) database, this paper constructs a panel data fixed effect model to explore the effects of spousal care on the health of middle-aged and older adult caregivers. Further, instrumental variables (IV) estimation and propensity score matching (PSM) are used to minimize the impacts of endogeneity.ResultsSpousal care has no significant effect on the physical health of middle-aged and older adult caregivers, but it has a significant negative effect on their mental health. Providing spousal care has a stronger negative effect on the mental health of female or rural middle-aged and older adult caregivers. The mechanism analysis shows that spousal care affects the mental health by reducing the number of weekly exercise and increasing the family’s non-food expenditure.ConclusionThe provision of spousal care in the middle-aged and older adult groups does harm the mental health of caregivers. Vulnerable groups such as families in which both spouses need care, female or rural caregivers expect more attention and support.

Roles of skin microbiota in hidradenitis suppurativa: insights from a two-sample mendelian randomization analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with unique lesional dysbiotic features. However, the role of the microbiology in the pathogenesis of HS remains in dispute. We aimed to conduct a two-sample Mendelian randomization study to investigate the relationship between skin microbiota and HS. A two-sample Mendelian randomization study was performed using the summary statistics of skin microbiota from summary GWAS data of the European descent from two cross-sectional, population-based German cohorts, KORA FF4 (n = 324) and PopGen (n = 273). The summary statistics of hidradenitis suppurativa were obtained from the FinnGen DF10 (1,070 cases and 394,105 controls). Inverse variance weighted (IVW), MR-Egger regression, weighted median, simple mode, weighted mode, and MRPRESSO were used to examine the causal association between skin microbiota and hidradenitis suppurativa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. Our study suggested that genus Corynebacterium in dry skin is significantly associated with HS after false discovery rate (FDR) correction (odds ratio (OR) = 1.04, 95% confidence interval (CI): 1.02-1.06, P = 0.0002, FDR adjusted P = 0.035). Additionally, we found genus Micrococcus in moist skin (OR = 1.10, 95% CI: 1.03-1.18, P = 0.0060, FDR adjusted P = 0.360), species Streptococcus salivarius in dry skin (OR = 1.03, 95% CI: 1.01-1.05, P = 0.0070, FDR adjusted P = 0.360), and species Propionibacterium granulosum (OR = 1.02, 95% CI: 1.00-1.04, P = 0.0460, FDR adjusted P = 0.970) are potentially associated with HS before FDR adjustment. No evidence of the effect in the reverse direction for HS on skin microbial features. This two-sample Mendelian randomization study found that genus Corynebacterium was causally associated with HS. Further studies are needed to clarify the protective effect of prebiotics, probiotics or microbiome transplants on HS.

Latent Association Between Diets and Glioma Risk: A Mendelian Randomization Analysis

Background: Gliomas, particularly high-grade gliomas such as glioblastoma, represent a major challenge due to their poor prognosis. While dietary factors have been proposed as potential modulators of glioma risk, causal inference has been hindered by confounding and reverse causality in observational studies. This study employs Mendelian randomization to investigate the causal relationship between dietary factors and glioma risk. Methods: A two-sample MR framework was applied, utilizing genome-wide association study data for 22 dietary exposures and glioma risks, including both GBM and non-GBM subtypes. Instrumental variables (genetic variants) were identified for each dietary factor to address confounding and pleiotropy. Causal inference was conducted using inverse-variance weighted regression, complemented by MR-Egger and MR-PRESSO analyses to assess and correct for potential pleiotropy. Results: A positive causal association was observed between the intake of cooked vegetables and the GBM risk (OR = 6.55, 95% CI: 1.86–23.12, p = 0.00350). While alcohol intake demonstrated a protective effect for non-GBM risk (OR = 0.770, 95% CI: 0.61–0.97, p = 0.029), beer was substantially linked to an increased risk of non-GBM gliomas (OR = 4.82, 95% CI: 1.84–12.59, p = 0.0014). Other dietary factors did not exhibit significant causal associations. Conclusions: These findings suggest that certain dietary factors, including cooked vegetable intake, beer consumption, and alcohol intake, may exert a causal influence on glioma risk. This study provides new insights into the potential dietary determinants of glioma and underscores the need for further investigation into modifiable risk factors for glioma prevention.

Relationship of Depression and Asthma: A Observational and Mendelian randomization study.

BackgroundBoth depression and asthma have a significant impact on the quality of life for individuals. Studies have shown that patients with depression often experience comorbid asthma; however, the precise relationship between these two conditions remains unclear. The objective of this study is to investigate the causal relationship between depression and asthma.MethodsIn a cross-sectional study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 and employed logistic regression to assess the correlation between depression and asthma. In the subsequent Mendelian randomization (MR) analysis, we selected single nucleotide polymorphisms (SNPs) closely linked to both depression and asthma as instrumental variables, based on summary data from genome-wide association studies (GWAS). The inverse variance weighted method (IVW) was then applied to ascertain the causal relationship between depression and asthma.ResultsBased on the results of the cross-sectional study, it was found that the status of depression was significantly associated with a higher risk of asthma (OR = 2.15, 95%CI = 1.79 ∼ 2.59, P < 0.001). Furthermore, in the MR analysis, a causal relationship was further identified between depression, severe depression, and the increased incidence of asthma (OR = 1.11, 95%CI = 1.05 ∼ 1.18, P < 0.001), (OR = 1.01, 95%CI = 1.01 ∼ 1.02, P < 0.001); the results of the reverse MR analysis indicated no causal relationship between asthma and the increased incidence of depression and severe depression (OR = 1.01, 95%CI: 0.99 ∼ 1.03, P = 0.50), (OR = 1.07, 95%CI: 0.82 ∼ 1.40, P = 0.64).ConclusionThis study has revealed a causal relationship between depression and an increased risk of developing asthma, offering new insights for the clinical intervention of both asthma and depression.

Do xenophobic attitudes influence migrant workers' regional location choice?

This paper investigates whether xenophobic attitudes, as measured by the regional share of votes for right-wing parties and xenophobic violence, affect migrants' choices of where to live in Germany. We use a unique panel data set for the period 2004 to 2017 and apply fixed effects regression models and instrumental variable estimation to examine the relationship between anti-immigrant attitudes and immigration. Our results indicate that xenophobic attitudes tend to reduce regional labour immigration. However, evidence seems to be more robust for the support of right-wing parties than for xenophobic violence. Regarding heterogeneous effects across skill groups, the findings are ambiguous. While the immigration of skilled workers seems to be more sensitive to xenophobic violence, evidence is more robust for the share of right-wing votes in the case of low-skilled foreign workers. The strength of the adverse effect of anti-immigrant attitudes tends to increase with the local size of the coethnic community.

Can vertical interlocks of executives block adverse loops between R&amp;D investment and the cost of equity capital? Evidence from China

Purpose This paper aims to conduct research on the role of vertical interlocks of executives in blocking adverse loops between research and development (R&amp;D) investment and the cost of equity capital and explore the action path of vertical interlocks of executives. This paper also analyzes the differences in the effect of vertical interlocks of chairman, vertical interlocks of chief executive officer (CEO) and vertical interlocks of CEO duality. Design/methodology/approach This paper uses 28,078 firm-year samples from Chinese A-share listed companies to study the impact of R&amp;D investment on the cost of equity capital using univariate group analysis and multiple regression methods. This paper analyzes the role of vertical interlocks of executives in reducing the positive impact of R&amp;D investment on the cost of equity capital by constructing interaction variables, by using group testing method to analyze the differences in the vertical interlocks of executives. This study also uses propensity score matching and instrumental variables to conduct robustness tests. Findings The vertical interlocks of executives can block adverse loops between R&amp;D investment and the cost of equity capital. The role of executive vertical interlocks is more prominent in non-state-owned firms, mainly exerting the resource effect that supports the innovation of non-state-owned firms, including the information resource effect and the financial resource effect. Through heterogeneity analysis, this paper discovered that the role of vertical interlocks of chairman is greater than that of the CEO and the CEO duality. Originality/value Based on the perspective of the correlation effect generated by vertical interlocks of executives, this paper analyzes the path of promoting corporate innovation. This provides new empirical evidence for studying the collaborative governance effect of vertical interlocks of executives “supervision effect, financial resource effect and information resource effect.” This study provides useful insights for regulatory authorities to regulate and guide development of the vertical interlocks of executives.

Association of workforce participation with depression among US older adults: results from NHANES 2005-2018.

The challenges of global aging would boost more workforce participation of older adults, and depression rate was increasing among older adults. This study aimed to explore the associations of workforce participation with depression among US older adults. This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Depression was measured with Patient Health Questionnaire-9 items (PHQ-9). Workforce participation was measured with work status, work types, shift work, and hours worked per week. Multivariate generalised linear and logistic regression models, also with restricted cubic spline (RCS) were performed to examine linear or non-linear associations between workforce participation and depression. Analyses of subgroup and sensitivity were conducted: using data from non-multiple imputation, participants aged over 65, and all non-excluded participants aged 60 or above to execute repeated analysis; recruiting propensity score matching (PSM) method that focused on selected SDoH, lifestyle, and health status-related factors to strengthen essential comaparability between workers and non-workers; employing two-stage least squares (2SLS) model and setting retirement age (over 65 years or not) as an instrumental variable (IV) to solve the potential reverse causation between work status and depression. A total of 10,312 participants aged 60 or above were enrolled with a prevalence of depression of 6.4%. There was a significantly negative association of PHQ-9 score with working (Exp [β] = 0.68; 95%CI: 0.53-0.87), working as private employee (Exp [β] = 0.67; 95%CI: 0.50-0.89), or working on regular daytime (Exp [β] = 0.65; 95%CI: 0.52-0.82). Especially, regular daytime working reduced depression risk by 52% compared with those who not working (OR = 0.48; 95%CI: 0.27-0.87). A significant decreased PHQ-9 score and depression risk as hours worked per week increased until reaching 34.86 and 25.35 in the RCS for generalised linear and logistic regression models, respectively. These effects were consistent across the analyses of subgroup and sensitivity. Regular daytime working was positively related to decreased depression risk among US older adults, and the suggested optimal working hours were 25 to 35 per week. Policymakers should appreciate the potential value of moderate workforce participation to mental health among older adults.

Exploring the genetic correlation and causal relationships between breast cancer and meningioma using bidirectional Mendelian randomization.

Previous studies have indicated a significantly higher prevalence of breast cancer (BC) among female patients with meningioma compared to the general female population. Therefore, this study aimed to assess the causal relationship between BC and meningioma at the genetic level. Genetic instrumental variables (IVs) for BC were identified from the Breast Cancer Association Consortium (BCAC), the Discovery Biology and Risk of Inherited Variants in Breast Cancer Consortium (DRIVE), the Collaborative Oncological Gene-environment Study (iCOGS), and 11 other BC genome-wide association studies (GWAS). Meningioma GWAS data were obtained from the FinnGen consortium and were further divided into intracranial and spinal meningioma groups for analysis. The primary analysis employed the inverse-variance weighted (IVW) method, supported by sensitivity analysis to address pleiotropy and enhance robustness. Next, linkage disequilibrium score regression (LDSC) was used to assess the genetic correlation between BC and meningioma. Finally, we applied the Functional Mapping and Annotation (FUMA) platform to conduct an in-depth analysis of the GWAS data. After rigorous screening and Mendelian randomization (MR) tests, genetically predicted overall BC (OR: 1.17, P = 0.0045) and ER(estrogen receptors) + BC (OR: 1.21, P = 0.0006) showed a potential causal association with intracranial meningioma. No causal relationships were found between intracranial meningioma and three BC subtypes. No bidirectional causal relationships were found between spinal meningioma and any BC subtype. The LDSC results suggested a modest positive genetic correlation between overall BC (rg: 0.152, SE: 0.077, P = 0.048), ER + BC (rg: 0.181, SE: 0.086, P = 0.035), and intracranial meningioma. FUMA analysis identified PITPNB, TTC28, and CHEK2 as shared risk genes between overall BC, ER + BC, and intracranial meningioma. These findings suggest that BC, especially ER + BC, may be a risk factor for intracranial meningioma. ER-related signaling pathways and the regulation of DNA damage may play a critical role in the pathogenesis of both diseases.

Can Enterprise Digitalization Promote Green Technological Innovation? Evidence from China’s Manufacturing Sector

China’s manufacturing industry is characterized by high energy consumption and high pollution, which urgently requires resolution through green technological innovation. This study focuses on China’s A-share listed manufacturing enterprises to explore their development path for green technological innovation. The study primarily employs statistical regression analysis to uncover the causal link between digitalization and green technology innovation. The study’s conclusion indicates that the digitalization of manufacturing enterprises has significantly promoted green technological innovation. This conclusion remains robust after a series of tests, including alternative variable measurements, instrumental variable (IV) estimation, and counterfactual analysis. Mechanism analysis reveals that digitalization can enhance green technological innovation by improving human capital and innovating business models. The results of the heterogeneity analysis show that the effect of digitalization on promoting green technological innovation is more pronounced in enterprises with higher green awareness among senior executives, high green credit, non-heavy pollution industries, a higher level of existing green technological innovation, and larger enterprise scale. The government should increase support for the digital transformation of enterprises and promote green technological innovation by enhancing the green awareness of enterprise senior executives, optimizing green credit policies, formulating transformation policies for heavily polluting enterprises, implementing differentiated policies based on enterprise scale, and promoting digital transformation.

Decline of Interest Rates under Inflation Targeting and Previous Regimes: Evidence from Latin America and Developed Countries

This study empirically investigates the impact of Inflation Targeting (IT) on nominal interest rates over the past 40 years, focusing on 10 advanced and emerging economies. By using a Binary Regime Model embedded within a Backward-Looking Taylor, our findings confirm that IT adoption has significantly contributed to reducing interest rates, with the strongest effects observed in Latin American countries. To reinforce these results, we incorporate Smooth Transition Regression (STR) models, with and without instrumental variables, allowing for a more suitable representation of gradual policy transitions. The STR estimates consistently support our main findings, validating the robustness of the observed impacts. Furthermore, we show that, both before and after IT implementation, central banks display a stronger emphasis on responding to inflation than to the output gap, with this focus intensifying under IT regimes.

Modifiable lifestyle factors and risk of intracranial aneurysm: A univariate and multivariate Mendelian randomisation study.

The aim of this study was to assess the potential causal relationship between lifestyle factors and intracranial aneurysms (IAs) using a two-sample Mendelian randomization (MR) approach. The study used a pooled dataset from a genome-wide association study that covered information on 24 lifestyle factors, intracranial aneurysm cases, subarachnoid hemorrhage, and unruptured aneurysms. Five MR methods were applied for analysis by selecting single nucleotide polymorphisms as instrumental variables, with the inverse variance weighting method as the main method. To ensure the stability of the results, horizontal multiple validity tests, sensitivity analyses, and inverse MR were performed, and genetically determined exposure factors were adjusted by multivariate MR. Several lifestyle factors were found to have a significant genetic causal effect on the occurrence and development of intracranial aneurysms. For example, lamb intake, smoking initiation, number of cigarettes smoked per day, length of television viewing, and fatigue were identified as genetic risk factors and strongly associated with aneurysm rupture, whereas red wine intake showed some genetic protection against intracranial aneurysms and similarly affected aneurysm rupture. Sensitivity analyses and inverse MR verified the robustness of these results. After adjusting for exposure factors, multivariate MR confirmed daily smoking and smoking initiation as risk factors for intracranial aneurysms, unruptured aneurysms, and subarachnoid hemorrhage, whereas red wine intake was a genetically protective factor against intracranial aneurysms and subarachnoid hemorrhage. This MR analysis revealed a genetic causal link between specific lifestyle factors and intracranial aneurysms, emphasizing the need for further studies to confirm these findings and explore their mechanisms.

Exploring the role of inflammatory biomarkers in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disorder with complex etiology. Inflammation has been suggested as a contributing factor to TN pathogenesis. This study investigates the causal relationship between inflammatory biomarkers, including 41 circulating inflammatory cytokines, C-reactive protein (CRP), and procalcitonin (PCT), and TN using Mendelian randomization (MR) analysis. A two-sample MR approach was employed using genome-wide association study (GWAS) data from 8293 Finnish individuals for inflammatory cytokines and data from the FinnGen database for TN. Instrumental variables (IVs) were selected based on genome-wide significance and clumping thresholds to avoid linkage disequilibrium. Inverse variance weighting (IVW) was used as the primary method, complemented by MR Egger regression, weighted median, simple mode, and weighted mode methods. Additionally, Bayesian Weighted MR (BWMR) and Multivariable MR (MVMR) were utilized to validate the findings and explore potential confounders. The present MR analysis identified significant causal associations for three inflammatory cytokines with TN. Stem cell growth factor beta (SCGF-β) (OR=1.362, 95% CI=1.049-1.770, p=0.021) and Interleukin-4 (IL-4) (OR=1.533, 95% CI=1.014-2.316, p=0.043) were positively associated with TN, while Interleukin-16 (IL-16) (OR=0.720, 95% CI=0.563-0.921, p=0.009) had a protective effect. CRP levels were also linked to TN risk (OR=0.751, 95% CI=0.593-0.951, p=0.017). No significant causal effect of PCT on TN was observed. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of horizontal pleiotropy or heterogeneity. This study highlights specific inflammatory biomarkers that may play pivotal roles in TN pathogenesis. SCGF-β and IL-4 are potential therapeutic targets due to their facilitative effects on TN, while IL-16 could offer protective benefits. CRP's association with TN further supports the involvement of systemic inflammation in this condition. These findings provide novel insights into TN's inflammatory mechanisms, suggesting new avenues for targeted interventions.

Association between chronic obstructive pulmonary disease and osteoporosis: Mendelian randomization combined with bibliometric analysis

BackgroundPrevious observational studies have reported an association between chronic obstructive pulmonary disease (COPD) and osteoporosis (OP). The aim of this study is to investigate the causal relationship between COPD and OP by two-sample Mendelian randomization (MR) analysis. The current status of cross-sectional research between COPD and OP in the past decade was explored through bibliometrics.MethodsSingle nucleotide polymorphisms (SNPs) that have been found to be strongly associated with COPD were used as instrumental variables (IVs) in MR Analysis. The primary outcome of the study was BMD measurement at five specific anatomical sites, namely the whole body, femoral neck, lumbar spine, forearm, and heel. These BMD measurements were derived primarily from a genome-wide association study (GWAS) and summary statistics from the International Genetic Factors Consortium for Osteoporosis (GEFOS). The main analysis method was inverse variance weighting (IVW). Multiple sensitivity analyses were performed to assess the robustness and reliability of the current MR Results. Further confirmatory MR Analysis between COPD and OP was applied. In bibliometrics. Publications were extracted from the Web of Science core collection publications related to osteoporosis and sarcopenia published between January 2014 and October 2024; Bibliometrics and visualization were performed by Microsoft Office Excel, Citespace, and R (Bibliometrix).ResultsThe MR Findings suggest that there is no causal relationship between COPD and BMD at five specific anatomical sites. The results of the primary IVW MR Analysis were generally supported by our sensitivity MR Analysis. We performed MR Analysis for the validation of COPD and OP (IVW OR: 1.019; 95%CI: 0.898–1.564; p = 0.768) also did not support a causal relationship between COPD and BMD. A total of 471 articles written by 1119 organizations from 42 countries/regions by 3331 authors and published in 238 journals were identified in the bibliometric analysis. China is the leading country in terms of the number of publications. China Medical University contributed the most publications. The International Journal of Chronic Obstructive Pulmonary Disease has the highest publication in this field.ConclusionsIn conclusion, This MR Study found no causal relationship between COPD and OP, suggesting that the observed associations may be due to common genetic effects or environmental confounders. The global research trends in this field in the past decade were summarized through bibliometric analysis, and care became the focus of future research on the relationship between copd and OP.

Causal association of inflammation with ischemic stroke and its subtypes: a bidirectional Mendelian randomization study.

Emerging evidence underscores a bidirectional relationship between ischemic stroke (IS) and inflammation, yet the causality of this association remains uncertain. We conducted a two-sample bidirectional Mendelian randomization (MR) study aimed at investigating the causal links between inflammation and IS. Single nucleotide polymorphism from genome-wide association studies of 112 inflammatory cytokines and IS were chosen as instrumental variables. We evaluated the causal effects of inflammatory factors on IS outcomes and examined the mediating effects of risk factors for IS. Additionally, reverse MR analysis was conducted to determine whether the occurrence of IS influenced levels of inflammatory cytokines. Causal associations were assessed using inverse variance weighting, complemented by sensitivity analyses incorporating weighted median and MR-Egger methods. We found associations between genetically predicted plasma levels of 25 inflammatory factors and IS along with its subtypes. MR supports smoking, body mass index, atrial fibrillation, coronary artery disease, heart failure, systolic blood pressure, diastolic blood pressure and type 2 diabetes as risk factors for IS. Notably, coronary artery disease and heart failure seemed to mediate the RANTES, HGF, IL-5 associations with IS. In addition, reverse MR analysis suggested a causal relationship between IS and its subtypes and 19 inflammatory factors. In summary, inflammation was suggestively causally associated with the risk of IS, and inflammatory cytokines had downstream effect on IS. Future studies should explore whether inflammatory factors found to have significant associations with IS risk could be manipulated to reduce IS risk, and the neuroinflammatory mechanisms after IS.