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Causal relationships of inflammatory cytokines and serum metabolites with colorectal carcinoma: A Mendelian randomization study 认领 引用 被引量：1
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作者 FENG Sisi XIAO Xiaomin +2 位作者 ZHOU Manli HUANG Zixin ZHONG Baiyun 《中南大学学报（医学版）》 CAS CSCD 北大核心 2026年第1期118-128,共11页
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat... Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC. 展开更多
关键词 inflammatory cytokines serum metabolites colorectal carcinoma Mendelian randomization genome-wide association study metabolomics analysis
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Methodological considerations in Mendelian randomization analyses of oral microbiota and cardiovascular disease 认领 引用
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作者 Abdullah Saad Ashal Waseem +1 位作者 Malaika Manzoor Anusha Tariq Kayani 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2026年第4期267-269,共3页
The important work of Qin,et al.[1]in investigating the association between oral microbiota and cardiovascular diseases using the Mendelian randomization approach is commendable,as it applies a contemporary genetic ep... The important work of Qin,et al.[1]in investigating the association between oral microbiota and cardiovascular diseases using the Mendelian randomization approach is commendable,as it applies a contemporary genetic epidemiological framework to address the longstanding challenges of confounding and reverse causation in microbiome research.By leveraging genomewide association data,the authors attempted to strengthen causal inference in an area largely dominated by observational evidence.Although the analysis is timely and methodologically ambitious,several issues warrant further consideration. 展开更多
关键词 mendelian randomization approach genomewide association datathe observational evidencealthough genetic epidemiological framework oral microbiota strengthen causal inference cardiovascular diseases mendelian randomization
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Cerebral Small Vessel Disease-driven Inflammatory Cytokines,Brain Structural Alterations,and Cognitive Function:A Mendelian Randomization Study 认领 引用
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作者 Mengxue Wang Zan Wang +4 位作者 Jingting Kong Lv Zhou Xuezi Zhang Yanjuan Wang Qingguo Ren 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2026年第6期662-676,共15页
Objective This study aimed to investigate the role of circulating inflammatory cytokines in the pathway linking cerebral small vessel disease(CSVD)to cognitive impairment(CI),and to further elucidate the neuroimaging ... Objective This study aimed to investigate the role of circulating inflammatory cytokines in the pathway linking cerebral small vessel disease(CSVD)to cognitive impairment(CI),and to further elucidate the neuroimaging mechanism of CSVD-driven inflammatory cytokines on cognitive function.Methods We conducted a two-step,two-sample Mendelian randomization(MR)analysis to evaluate the causal effect of CSVD on circulating inflammatory cytokines and CSVD-driven inflammatory cytokines on the risk of CI.Using a separate two-sample MR analysis,we explored the potential mechanisms by which these inflammatory cytokines affect cognition,with cytokines identified as mediators between CSVD and CI treated as exposure and brain structural imaging as outcomes.Results Genetically predicted CSVD was causally associated with the levels of 11 circulating inflammatory cytokines.Among these CSVD-driven inflammatory cytokines,growth-regulated oncogene alpha(GROα)was associated with poorer verbal and numerical reasoning,stem cell factor(SCF)was associated with better working memory,and tumor necrosis factor-alpha(TNF-α)was associated with reduced processing speed.SCF mediated the association between small-vessel ischemic stroke and numeric memory performance,with a mediation effect of 10%.Furthermore,circulating SCF levels showed causal relationships with the volumes of multiple brain regions within the default mode network and with the integrity of seven white matter tracts.Conclusion SCF,GROα,and TNF-α play important roles in the pathway linking CSVD to CI.Circulating SCF may influence cognitive function by modulating brain volume and white matter integrity. 展开更多
关键词 Cerebral small vessel disease Mendelian randomization Inflammation Cognitive impairment Neuroimaging
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Causal association between oral microbiota and hepatocellular carcinoma in East Asian populations:a Mendelian randomization study 认领 引用
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作者 ZHONG Hanxiang ZHAO Yuanyu +4 位作者 FU Hong DONG Jiayong DING Guoshan CHEN Yao GUO Wenyuan 《南方医科大学学报》 CAS CSCD 北大核心 2026年第7期1455-1461,共7页
Objective Emerging evidence highlights the crucial role of the oral microbiota in various malignancies,but its causal relationship with hepatocellular carcinoma(HCC)remains largely unexplored.This study aimed to inves... Objective Emerging evidence highlights the crucial role of the oral microbiota in various malignancies,but its causal relationship with hepatocellular carcinoma(HCC)remains largely unexplored.This study aimed to investigate the causal association between oral microbiota composition and HCC risk in East Asian populations using Mendelian randomization(MR)analysis.Methods We performed a two-sample Mendelian randomization to investigate the causal association of 309 tongue dorsum microbiomes and 285 salivary microbiomes with liver cancer progression using the latest pooled data from genome-wide association study(GWAS)of oral microbiomes in East Asian populations.We selected single nucleotide polymorphism(SNP)independent of confounders as the instrumental variable(IV)for causal inference analysis using various Mendelian randomization statistical techniques.The heterogeneity and pleiotropy of the IV was evaluated to ensure the reliability of the results.Results Our analysis revealed a complex association between specific bacterial genera in the oral microbiome and liver cancer.Streptococcus showed a mixed association with hepatocellular carcinoma,while Oribacterium and Centipeda showed a positive correlation with HCC occurrence.Gemella genus was negatively correlated with HCC.Heterogeneity or pleiotropy of the IV was not detected in the sensitivity analysis.Conclusion This study provides the first Mendelian randomization evidence linking oral microbiota to HCC susceptibility in East Asian populations.Our findings suggest causal roles of specific oral bacterial taxa in hepatocarcinogenesis,and offer new insights into the mechanisms of the oral-liver axis and potential microbial targets for HCC prevention and treatment. 展开更多
关键词 causal association oral microbiota Mendelian randomization hepatocellular carcinoma East Asian populations
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Integration of Single-cell RNA Sequencing and Mendelian Randomization Analysis for Identifying Potential Immune Therapeutic Targets in Amyotrophic Lateral Sclerosis 认领 引用
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作者 Xinyuan Pang Hongfen Wang +1 位作者 Jiongming Bai Xusheng Huang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2026年第3期327-341,共15页
Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal lin... Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+cytotoxic T cell-related genes and ALS risk.Methods Single-cell RNA sequencing(scRNA-seq)of peripheral blood mononuclear cells(PBMCs)from patients with ALS and healthy controls(HC)was used to identify differentially expressed genes(DEGs)in CD4+cytotoxic T cells.Comprehensive analyses of CD4+cytotoxic T cells,including pseudotemporal trajectory,intercellular communication,and metabolic pathway analysis,were performed.Mendelian randomization(MR)analysis evaluated the causal effects of DEGs on ALS risk,with validation using independent genome-wide association study(GWAS)data.Expression patterns of the causal genes were further verified using scRNA-seq,bulk-seq,and clinical samples.Results CD4+cytotoxic T cells were significantly expanded in patients with ALS.The upregulated genes S100A6,SERPINB6,SMAD7,and TPST2 were positively correlated with ALS susceptibility,whereas DIP2A showed a protective association.Conclusion S100A6,SERPINB6,SMAD7,TPST2,and DIP2A were identified as causal genes and potential therapeutic targets in ALS,implicating CD4+cytotoxic T cells in the disease mechanisms.Further studies targeting these genes and neuroinflammatory pathways are warranted. 展开更多
关键词 Amyotrophic lateral sclerosis CD4+cytotoxic T cells Drug target Mendelian randomization Single-cell RNA sequencing
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Higher BMI might increase risk of ankle–foot sprains:A mendelian randomization study 认领 引用
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作者 Xicheng Gu Xiao'ao Xue +3 位作者 Yi Li Ziyi Chen He Wang Yinghui Hua 《Sports Medicine and Health Science》 CAS CSCD 2026年第3期302-310,共9页
Purpose:Although previous research has suggested that a greater body mass index(BMI)may be linked to a higher incidence of ankle–foot sprains,the causal relationship between BMI and these injuries has not been establ... Purpose:Although previous research has suggested that a greater body mass index(BMI)may be linked to a higher incidence of ankle–foot sprains,the causal relationship between BMI and these injuries has not been established.This study aims to determine the causal effect of BMI-related features on ankle–foot sprains using a two-sample Mendelian randomization(MR)analysis.Methods:Exposure single-nucleotide polymorphisms were collected from Genetic Investigation of Anthropometric Traits(GIANT Consortium)for BMI,hip circumference(HIP),hip circumference adjusted for BMI(HIPadjBMI),waist circumference(WC),waist circumference adjusted for BMI(WCadjBMI),waist-to-hip ratio(WHR),and waistto-hip ratio adjusted for BMI(WHRadjBMI),encompassing a study population of more than 200000 individuals.Furthermore,exposure statistics were gathered from MEC-IEU for body fat percentage(BFP),involving a study population of 454633 individuals.Additionally,outcome statistics for ankle sprains were identified from FinnGen based on hospital discharge records(9141 cases and 290508 healthy controls).Random-effect,inverse-variance weighted MR was used as the primary method.Results:BMI(β=0.173,p=0.035),BFP(β=0.341,p=9.08×10-6),hip circumference(β=0.265,p=0.001),and WC(β=0.193,p=0.045)were found to have positive causal relationships with higher risk of ankle–foot sprains,whereas HIPadjBMI,WCadjBMI,WHR,and WHRadjBMIwere found to have no such effect.Additionally,no reverse causal effect was found between ankle–foot sprains and BMI or BFP.Conclusions:A genetic predisposition to higher BMI-related features can lead to a higher risk of ankle–foot sprains,providing new insight into how to prevent ankle–foot sprains in middle-aged and elderly people. 展开更多
关键词 Ankle injuries Body mass index Body fat percentage Mendelian randomization analysis
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Causal effect of obesity on cataract and mediating roles of metabolites:a Mendelian randomization study 认领 引用
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作者 Chen Li Jiao-Man Wang Wei-Hua Yang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第3期564-574,共11页
AIM:To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization(MR).METHODS:Summary-level data from large-scale genome-wide asso... AIM:To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization(MR).METHODS:Summary-level data from large-scale genome-wide association studies to examine the relationship between obesity and cataract were utilized.Obesity-related traits,including body mass index(BMI),waist-to-hip ratio(WHR),and waist circumference(WC).A two-sample MR approach was employed to assess the causal effect of obesity on cataract risk,while potential mediators were identified from suitable genome-wide association studies(GWAS)datasets.Additionally,a metabolic pathway analysis was conducted.RESULTS:An increase of 1 standard deviation(SD)in BMI,WHR,and WC was associated with a significantly higher risk of cataract(BMI:odds ratio(OR)1.0017,95%confidence interval(CI):1.0001-1.0032,P=0.0320;WHR:OR 1.0029,95%CI:1.0006-1.0051,P=0.0129;WC:OR 1.0020,95%CI:1.0001-1.0038,P=0.0390].These associations remained robust after adjusting for confounding factors in multivariable MR analysis.Furthermore,a two-step MR analysis identified eight potential metabolic mediators,with one mediator showing a significant causal role in the relationship between obesity and cataract.CONCLUSION:This work highlights the importance of addressing obesity as a modifiable risk factor for cataracts,particularly through metabolic pathways. 展开更多
关键词 obesity cataract Mendelian randomization body mass index waist-to-hip ratio waist circumference
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Genetic evidence for associations between food intake and prostatic diseases:a Mendelian randomization study 认领 引用
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作者 Xiangyu Chen Congzhe Ren +1 位作者 Lijun Xie Xiaoqiang Liu 《The Canadian Journal of Urology》 SCIE 2026年第2期339-348,共10页
Background:Regional differences in the incidence of prostate cancer(PCa)and prostatitis may be due to different food intake.But which foods affect PCa and prostatitis development or progression remains controversial.T... Background:Regional differences in the incidence of prostate cancer(PCa)and prostatitis may be due to different food intake.But which foods affect PCa and prostatitis development or progression remains controversial.This study aims to explore the causal relationship between PCa and prostatitis and 30 different foods using two-sample Mendelian randomization(MR)and multivariable MR(MVMR)analysis.Methods:Data on 30 different foods were screened from the UK Biobank.PCa data came from a large metaanalysis of 140,254 individuals;prostatitis was obtained from the FinnGen consortium.The inverse variance weighted method was the main analysis method.MREgger,Cochran’s Q,radialMR,andMR-PRESSO tests were used for sensitivity analysis.Results:Our results demonstrated that never eating sugar[odds ratio(OR),0.30;95%confidence interval(CI),0.11–0.80;p=0.02]and never eating eggs(OR,0.52;95%CI,0.28–0.97;p=0.04)reduced the risk of PCa;raw vegetable intake(OR,2.27;95%CI,1.01–5.09;p<0.05)and dried fruit intake(OR,1.38;95%CI,1.02–1.87;p=0.04)increased PCa risk.And a negative correlation existed between processed meat intake and prostatitis(OR,0.27;95%CI,0.08–0.94;p=0.04).After adjusting for smoking and drinking,never eating sugar was negatively correlated with PCa,while the raw vegetable intake was positively correlated with the risk of PCa.Conclusion:Our study found four different foods associated with PCa and one food intake associated with prostatitis.We recommend more high-quality studies to reassess the benefits of individual foods in PCa. 展开更多
关键词 Individual foods prostate cancer prostatitis Mendelian randomization
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Genetic and biological determinants of pulmonary embolism:Insights from Mendelian randomization studies 认领 引用
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作者 Rupak Desai Darsh Patel +9 位作者 Abhishek Prasad Navya Mandalapu Jai Nagarajan Ananth Guddeti Sourabh Khatri Warda Shahnawaz Abdul Aleem Adil S Mohammed Umera Yasmeen Muhammad Usman Ghani 《World Journal of Experimental Medicine》 2026年第2期13-24,共12页
Pulmonary embolism(PE)is a common and potentially fatal thromboembolic disease contributing to a major global public health burden.Its pathogenesis involves multiple hemodynamic,inflammatory,metabolic,and genetic fact... Pulmonary embolism(PE)is a common and potentially fatal thromboembolic disease contributing to a major global public health burden.Its pathogenesis involves multiple hemodynamic,inflammatory,metabolic,and genetic factors.The multifactorial nature of PE makes it difficult to infer the direct effects of risk factors using conventional statistical approaches because of potential confounding and reverse causality.Mendelian randomization(MR)uses genetic variants as instrumental variables to strengthen causal inference.This narrative review synthesizes the available MR literature concerning potential causative factors of PE,with particular emphasis on genetic and biological pathways.MR evidence suggests that matrix metalloproteinases(MMP)-19 may be associated with increased PE susceptibility,whereas MMP-12 may be associated with decreased susceptibility.Impaired kidney function showed a positive association with PE risk,and reduced HLA-DR+NK cell traits were linked to PE pathogenesis.Among gut microbiota,Clostridium innocuum was associated with increased PE risk,whereas Butyricicoccus and Actinobacteria showed protective associations.No consistent causal associations were identified for type 2 diabetes,atrial fibrillation,or epigenetic age acceleration.Larger multiethnic studies integrating multi-omics data are needed to clarify mechanisms underlying PE pathogenesis. 展开更多
关键词 Pulmonary embolism Mendelian randomization Matrix metalloproteinases Immune dysregulation Renal dysfunction Genetic epidemiology Thrombosis Risk factors
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Evaluating the association between oral microbiota and cardiovascular diseases: evidence from Mendelian randomization analysis 认领 引用 被引量：1
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作者 Si-Da QIN Yi-Wen ZHANG Jing-Zhi WANG 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2026年第1期36-44,共9页
Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular ... Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular disease risk,including atrial fibrillation,myocardial infarction,chronic heart failure,and hypertension.Methods We analyzed GWAS data from East Asian populations'oral microbiome,involving 2,017 tongue and 1,915 saliva samples from 2,984 individuals with whole-genome sequencing.Additionally,we sourced cardiovascular disease GWAS data from NBDC,including atrial fibrillation(8,180 cases,28,621 controls),myocardial infarction(14,992 cases,146,214 controls),chronic heart failure(10,540 cases,168,186 controls),and systolic blood pressure(145,505 individuals).Results Several oral microbiota taxa were found to be significantly associated with cardiovascular disease outcomes.Specific microbiota,such as Centipeda,Corynebacterium,and Pseudomonas E,were negatively correlated with heart failure.In contrast,taxa like Neisseria D and Actinomyces were associated with an increased risk of atrial fibrillation and myocardial infarction.Additionally,certain oral microbiota showed correlations with changes in blood pressure,highlighting their potential role in hypertension.Conclusion Our findings suggest that the oral microbiota may influence the development and progression of cardiovascular diseases,providing new insights into the potential impact of oral health on cardiovascular risk. 展开更多
关键词 cardiovascular disease oral microbiota oral microbiome gwas data Mendelian randomization atrial fibrillation atrial fibrillationmyocardial
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Bidirectional Mendelian Randomization and Colocalization Study of Memory B Cells and Major Depressive Disorder 认领 引用
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作者 Shao-meng Si Yue-yang Xin +5 位作者 Shao-di Guan Jie Dong Pei Lu Hao Chen Wei Xia Hui Xu 《Current Medical Science》 SCIE CAS CSCD 2026年第1期264-273,共10页
Objective Emerging evidence implicates neuroinflammation in the pathogenesis of major depressive disorder(MDD),yet the role of memory B cells remains unclear.In this study,we conducted a bidirectional two-sample Mende... Objective Emerging evidence implicates neuroinflammation in the pathogenesis of major depressive disorder(MDD),yet the role of memory B cells remains unclear.In this study,we conducted a bidirectional two-sample Mendelian randomiza-tion(MR)study and Bayesian colocalization analyses to investigate the causal relationships between memory B-cell traits and MDD risk.Methods MDD summary data were gathered from a meta-analysis of genome-wide association studies(GWASs),whereas memory B-cell genetic variations were sourced from GWASs on immune phenotypes.MR analysis utilized the inverse variance weighted(IVW),MR-Egger,and weighted median methods.Moreover,various sensitivity analyses,including Cochran's Q test,MR Pleiotropy Residual Sum and Outlier(MR-PRESSO),MR-Egger intercept test and Leave-one-out(LOO)analysis,were performed to confirm MR result stability.Bayesian colocalization analyses were also conducted to identify genetic loci shared between memory B cells and MDD.Results Our results indicated that genetically predicted increased CD27 protein expression on memory B cells causally elevated MDD risk(ORs:1.025-1.063,PFDR<0.05).Conversely,MDD did not causally affect memory B-cell traits.Addi-tionally,the colocalization analysis revealed no shared genetic variants,suggesting distinct biological pathways.Conclusions These findings highlight CD27 as a potential novel biomarker and therapeutic target in MDD,warranting fur-ther clinical validation in the future. 展开更多
关键词 Major depressive disorder Memory B cells Mendelian randomization Colocalization analysis Neuroinflammation CD27 Immunopsychiatry B cell activation
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Dissecting the Causal Association between Body Fat Mass and Obsessive-Compulsive Disorder:A Two-Sample Mendelian Randomization Study 认领 引用
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作者 Meiling Hu Zhennan Lin +2 位作者 Hongwei Liu Yunfeng Xi Youxin Wang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2026年第1期36-45,共10页
Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association betw... Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition. 展开更多
关键词 Mendelian randomization Body fat mass Obsessive-compulsive disorder Causal inference
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Causal relationships between 41 inflammatory cytokines and myopia:a Mendelian randomization study 认领 引用
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作者 Xiao-Fei Wu Lei Yu +3 位作者 Ying Zhang Shuang Li Rui Li Lian-Yi Sun 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第3期575-581,共7页
AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)da... AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia. 展开更多
关键词 myopia inflammatory cytokines Mendelian randomization causal association single nucleotide polymorphism genome-wide association study
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Exploration of the association of antidiabetic drugs with urolithiasis:A drug-targeted Mendelian randomization study 认领 引用
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作者 Xidong Wang Qiancheng Mao +3 位作者 Tianqi Wang Yingying Yang Ming Liu Jitao Wu 《Asian Journal of Urology》 CAS CSCD 2026年第1期56-66,共11页
Objective:Type 2 diabetes mellitus has previously been reported to be potentially associated with urolithiasis.We conducted a Mendelian randomization(MR)study to explore whether there is a causal relationship between ... Objective:Type 2 diabetes mellitus has previously been reported to be potentially associated with urolithiasis.We conducted a Mendelian randomization(MR)study to explore whether there is a causal relationship between genetic susceptibility to common antidiabetic drugs and urolithiasis risk.Methods:We used genetic variants from two different sources as instruments to proxy the exposure to antidiabetic drugs for our MR research design.The variants included loci regulating expression traits of the target genes,and genetic variants associated with blood glucose nearby or within antidiabetic drug target genes from genome-wide association studies.We ultimately calculated estimates using inverse-variance weighted MR(IVW-MR)and summarydata-based MR methods.Results:The Bonferroni-corrected IVW results suggested potassium inwardly rectifying channel subfamily J member 11(KCNJ11)-mediated blood glucose was associated with a lower risk of urolithiasis(odds ratio[OR]:0.15;95% confidence interval[CI]:0.06-0.39;p=1.19×10-4).Similarly,we also observed a higher expression of KCNJ11 was linked to a decreased risk of urolithiasis in the summary-data-based MR analysis(OR:0.81 per 1 mmol/L decrement in blood glucose;95%CI:0.70-0.95;p=0.008).We found suggestive evidence of the positive relationship between insulin receptor expression and urolithiasis(OR:5.67;95%CI:1.01e31.97;pZ0.049),which was not supported when using cis-expression quantitative trait locus as an instrument.Conclusion:This study provided evidence for a potential causal link between KCNJ11-mimicked sulfonylureas and the reduced risk of urolithiasis.Given the limitations of this study,it is essential to investigate further using the latest data from large-scale genetic studies and relevant clinical data to validate our findings from the MR study. 展开更多
关键词 Type 2 diabetes mellitus Antidiabetic drugs Summary-data-based Mendelian randomization Urolithiasis
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Two-sample Mendelian randomization study of gut microbiota and inflammatory proteins:Predictive,preventive,and personalized treatment for migraine 认领 引用
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作者 Ruolan Ma Haiyan An Yi Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第9期4474-4480,共7页
The human gut microbiota is increasingly recognized as a significant factor in the pathogenesis of migraine,potentially via inflammatory pathways.Identifying specific human gut microbiota components associated with mi... The human gut microbiota is increasingly recognized as a significant factor in the pathogenesis of migraine,potentially via inflammatory pathways.Identifying specific human gut microbiota components associated with migraines,along with the investigation of particular inflammatory proteins,is essential for advancing primary prediction,targeted prevention,and personalized treatment strategies for migraines.We conducted a two-sample Mendelian randomization study using publicly available summary statistics from genome-wide association studies.Data for 473 human gut microbiota taxa were obtained from the Finnish national health survey conducted by the National Institute for Health and Welfare study(FINRISK,n = 5959 European participants).Genome-wide association study data(http://gffzz7fe8ccc2a30242bfsx0vpufqwv0ub6fkv.ffgz.tsg.suse.edu.cn/gwas/) for 91 circulating inflammatory proteins were obtained from 14,824 participants across 11 cohorts using the Olink Target 96 Inflammation panel.Migraine outcome data were obtained from the FinnGen R12 release,with cases defined using ICD-10 code G43.All genome-wide association study analyses were adjusted for sex,age,genotyping batch,and 10 genetic principal components to control population stratification(genomic inflation factors:1.00-1.05).Inverse variance-weighted Mendelian randomization was the primary analysis method,with Mendelian randomization-Egger,weighted median,and mode-based methods as sensitivity analyses.Two-step Mendelian randomization mediation analysis quantified the proportion of the effects of human gut microbiota on migraine that are mediated through inflammatory proteins.Thirty-seven bacterial genera were found to be associated with migraine using the inverse variance-weighted method.Of these,18 genera exhibited a negative association,while 19 genera demonstrated a positive association with migraine risk.Additionally,eight inflammatory proteins were found to increase the risk of migraine.Among human gut microbiota,four were observed to reduce inflammatory protein levels,whereas another four were associated with increased inflammatory protein levels.Additionally,five gut microbiota were identified to influence migraine through inflammatory proteins in both Mendelian randomization analyses.Specifically,Actinobacteria,Brachyspiraceae,CAG-269 sp001915995,and Paraglaciecola were found to affect migraine outcomes via inflammatory proteins,with mediation proportions of 12%,19%,15.5%,and 6.7%,respectively.Lawsonibacter sp002161175 was identified to influence migraine risk through Oncostatin-M and SLAM,with mediation proportions of 15.6% and 11.3%,respectively.Our study elucidated the role of specific human gut microbiota alterations in the pathogenesis of migraine and highlighted the mediating effects of inflammatory proteins.Targeting these particular human gut microbiota alterations offers a promising strategy for predictive,preventive,and personalized medicine in migraine management,resulting in substantial clinical advancements. 展开更多
关键词 causality cytokines gut-brain axis human gut microbiota inflammation protein mediating proportion mediation mendelian randomization microbiome migraine
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Targeting obesity and lipid metabolism profiles to prevent perianal abscesses:A case-control study and Mendelian randomization analysis 认领 引用
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作者 Huang-Fu Ma Jia-Hua Qian +6 位作者 Yi-Hao Chen Yue Wang Yan-Mei Wang Jia-Nan Li Zhang-Yun Zhou Jian-Xiong Ma Xue-Cheng Zhang 《World Journal of Gastrointestinal Surgery》 SCIE 2026年第1期28-38,共11页
BACKGROUND Perianal abscesses(PAs)are associated with significant complications,such as recurrent infections,pain,anal fistulas,rectovaginal fistulas,rectourethral fistulas,and rectovesical fistulas.However,establishe... BACKGROUND Perianal abscesses(PAs)are associated with significant complications,such as recurrent infections,pain,anal fistulas,rectovaginal fistulas,rectourethral fistulas,and rectovesical fistulas.However,established primary and secondary prevention strategies for PAs are lacking.AIM To explore the relationships between obesity and lipid metabolites,including perianal abscess onset.METHODS We conducted two independent studies under a unified research question.Casecontrol analysis was conducted at a single hospital between May 2023 and November 2023.Inpatients diagnosed with a perianal abscess and matched healthy controls were included.Body dimensions and serum metabolites were measured.Genome-wide association study data regarding genetic variants of PAs,obesity,and serum metabolites were obtained for the Mendelian randomization(MR)analysis.The study outcomes were perianal abscess onset and the number and location of PAs.RESULTS In the case-control study,higher body mass index(BMI),waist-to-hip ratio(WHR),waist-to-height ratio(WHtR),blood glucose levels,uric acid(UA)levels,total cholesterol levels,triglyceride levels,and low-density lipoprotein(LDL)levels were associated with increased risk of PAs.Higher high-density lipoprotein levels were associated with reduced risk of PAs.The BMI,WHR,WHtR,UA level,triglyceride level,and LDL level were associated with the number and severity of PAs.In MR analysis,the BMI,WHR,body fat percentage,whole body fat mass,limb fat percentage,limb fat mass,and various lipid profiles were significantly associated with the risk of PAs.CONCLUSION A hospital-based case-control study and an independent MR analysis consistently support obesity and lipid metabolism profiles are associated with an increased risk of perianal abscess.These findings provide a basis for developing primary and secondary prevention strategies for perianal abscess. 展开更多
关键词 Perianal abscess Prevention Obesity Lipid metabolism profile Case-control study Mendelian randomization
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Association between asthma and myopia:the NHANES database and Mendelian randomization analysis 认领 引用
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作者 Ya-Jing Zheng Ji-Fa Kuang +1 位作者 Fei-Lan Chen Wen-Bin Huang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第1期132-139,共8页
AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 ... AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included.By exclusion criteria,8460 subjects were screened with 1676 myopia samples and 6784 control samples.Subsequently,baseline characteristics,association analyses,risk stratification analyses,and receive operating characteristic curve(ROC)were used to investigate the associations between covariates and myopia.Then,the causal relationship was explored in depth by MR analysis,and was estimated the reliability by sensitivity analyses and directionality tests.RESULTS:Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates(excluding gender;P1).ROC proved that the model was accurate in its prediction[area under curve(AUC)=0.7].Subsequently,the causal relationship between them was statistically significant(P1).The funnel plot demonstrated compliance with Mendel’s second law.Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.CONCLUSION:A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis,which is important implications for public health policy development and clinical practice. 展开更多
关键词 asthma myopia National Health and Nutrition Examination Survey Mendelian randomization
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Genetically predicted body mass index and self-reported hearing difficulty:a twosample Mendelian randomization study with external replication 认领 引用
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作者 Yubin Xue Hongwei Ma +1 位作者 Lin Yang Qiang Liu 《Journal of Otology》 CSCD 2026年第3期152-159,共8页
Background:Self-reported hearing difficulty is a common hearing-related complaint and may reflect perceived auditory impairment,communication difficulties,or clinically relevant hearing loss.Observational studies have... Background:Self-reported hearing difficulty is a common hearing-related complaint and may reflect perceived auditory impairment,communication difficulties,or clinically relevant hearing loss.Observational studies have linked cardiometabolic traits to hearing-related outcomes,but these asso-ciations are difficult to interpret because of residual confounding and reverse causation.Methods:We performed a two-sample Mendelian randomization(MR)study to evaluate the potential associations of five genetically predicted cardiometabolic traits-body mass index(BMI),C-reactive protein(CRP),systolic blood pressure(SBP),low-density lipoprotein cholesterol(LDL-C),and liability to type 2 diabetes(T2D)-with self-reported hearing difficulty.The primary outcome was self-reported hearing difficulty in the UK Biobank(field 2247;OpenGWAS:ebi-a-GCST90013961).External replication was conducted using a large genome-wide association meta-analysis of hearing loss/difficulty in hearing(OpenGWAS:ebi-a-GCST90018857).The inverse-variance weighted(IVW)method was prespecified as the primary estimator,complemented by sensitivity analyses and multivariable MR(MVMR)to assess robustness and the independence of the observed association.Results:Genetically predicted higher BMI was associated with higher odds of hearing difficulty in the primary analysis(IVW OR 1.076,95%CI 1.030-1.124;P=0.0011),and a directionally concordant association was observed in the external replication dataset(OR 1.092,95%CI 1.012-1.178;P=0.0226).By contrast,IVW estimates for CRP,SBP,LDL-C,and T2D liability were close to the null and showed no consistent evidence of association across the two outcome datasets.In MVMR including BMI and CRP,the BMI estimate attenuated toward the null,whereas CRP showed no independent association.Conclusions:These findings provide suggestive genetic evidence that higher BMI is associated with increased liability to self-reported hearing difficulty,whereas the other cardiometabolic traits examined showed limited evidence of consistent associations.However,the BMI association should be interpreted cautiously given the heterogeneity,pleiotropy-related findings,and attenuation observed in MVMR. 展开更多
关键词 mendelian randomization hearing difficulty body mass index cardiometabolic risk factors genome-wide association study
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Lifestyle behaviors,serum metabolites and high myopia:Mendelian randomization and mediation analysis 认领 引用
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作者 Nian-En Liu Xiao-Tong Xu Xiao-Bing Yu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第1期140-148,共9页
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy... AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations. 展开更多
关键词 high myopia physical activity serum metabolites multivariable Mendelian randomization mediation analysis
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The role of immune cells in mediating the effects and prognosis of lipidome in ER+breast cancer:A mendelian randomization study 认领 引用
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作者 Fenyan Chen Congting Hu +6 位作者 Pingping Peng Ziming Cai Suyan Liu Jia Liu Jiaqin Cai Xiaoxia Wei Hong Sun 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2026年第6期560-573,共14页
Previous studies have suggested a potential interplay between the lipidome and immune cell dynamics in the development of estrogen receptor-positive(ER+)breast cancer(BC);however,the causal contribution of specific li... Previous studies have suggested a potential interplay between the lipidome and immune cell dynamics in the development of estrogen receptor-positive(ER+)breast cancer(BC);however,the causal contribution of specific lipid species and their potential mediation through immune cells remain poorly defined.To address this gap,the present study leveraged large-scale genome-wide association study(GWAS)data covering 179 lipid species.Two-sample Mendelian randomization(TSMR)was employed as the primary analytical framework to systematically evaluate the causal effects of diverse molecular lipid subtypes on ER+BC risk,as well as on short-term(5-year)and long-term(15-year)survival outcomes.The robustness of the primary causal estimates was further examined using Bayesian weighted Mendelian randomization(BWMR),alongside comprehensive sensitivity analyses,including formal assessments of heterogeneity and horizontal pleiotropy.Our analyses revealed that several lipid classes,most notably diacylglycerol,phosphatidylcholine,phosphatidylethanolamine,phosphatidylinositol,and triacylglycerol,exerted significant causal effects on both ER+BC susceptibility and patient survival.In addition,29 immune cell phenotypes were identified as being associated with prognosis,among which five emerged as potential key mediators linking lipid metabolism to ER+BC survival.Collectively,these findings provided robust genetic evidence supporting a causal role of the lipidome in the pathogenesis and progression of ER+BC,with this effect appearing to be partially mediated by specific immune cell populations. 展开更多
关键词 ER+BC Lipidome Immune cell Mendelian randomization
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