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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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Bidirectional Mendelian randomization and mediation analysis of million-scale data reveal causal relationships between thyroid-related phenotypes,smoking,and lung cancer 认领 引用
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作者 Xiang Wang Xuan Wang +15 位作者 Mengsheng Zhao Lijuan Lin Yi Li Ning Xie Yanru Wang Aoxuan Wang Xiaowen Xu Can Ju Qiuyuan Chen Jiajin Chen Ruili Hou Zhongwen Zhang David C.Christiani Feng Chen Yongyue Wei Ruyang Zhang 《Journal of Biomedical Research》 CAS CSCD 2025年第5期441-451,I0001-I0023,共11页
Emerging evidence highlights the role of thyroid hormones in cancer,although findings are controversial.Research on thyroid-related traits in lung carcinogenesis is limited.Using UK Biobank data,we performed bidirecti... Emerging evidence highlights the role of thyroid hormones in cancer,although findings are controversial.Research on thyroid-related traits in lung carcinogenesis is limited.Using UK Biobank data,we performed bidirectional Mendelian randomization(MR)to assess causal associations between lung cancer risk and thyroid dysfunction(hypothyroidism and hyperthyroidism)or functional traits(free thyroxine[FT4]and normal-range thyroid-stimulating hormone[TSH]).Furthermore,in the smoking-behavior-stratified MR analysis,we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking behaviors and lung cancer.We demonstrated significant associations between lung cancer risk and hypothyroidism(hazard ratio[HR]=1.14,95%confidence interval[CI]=1.03–1.26,P=0.009)and hyperthyroidism(HR=1.55,95%CI=1.29–1.87,P=1.90×10-6)in the UKB.Moreover,the MR analysis indicated a causal effect of thyroid dysfunction on lung cancer risk(ORinverse variance weighted[IVW]=1.09,95%CI=1.05–1.13,P=3.12×10-6for hypothyroidism;ORIVW=1.08,95%CI=1.04–1.12,P=8.14×10-5for hyperthyroidism).We found that FT4 levels were protective against lung cancer risk(ORIVW=0.93,95%CI=0.87–0.99,P=0.030).Additionally,the stratified MR analysis demonstrated distinct causal effects of thyroid dysfunction on lung cancer risk among smokers.Hyperthyroidism mediated the effect of smoking behaviors,especially the age of smoking initiation(17.66%mediated),on lung cancer risk.Thus,thyroid dysfunction phenotypes play causal roles in lung cancer development exclusively among smokers and act as mediators in the causal pathway from smoking to lung cancer. 展开更多
关键词 hypothyroidism hyperthyroidism lung neoplasms smoking causality Mendelian randomization analysis
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Prognostic and therapeutic implications of lipid metabolism‑related lncRNAs in lung adenocarcinoma:a comprehensive analysis integrating transcriptomics,Mendelian randomization,and immunotherapy sensitivity 认领 引用
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作者 Xiao Zhu 《Clinical Cancer Bulletin》 2025年第1期144-159,共16页
Background and Aim Lipid metabolism plays a crucial role in cancer progression,and long non-coding RNAs(lncRNAs)are emerging as key regulators in tumor biology.However,the prognostic and therapeutic implications of li... Background and Aim Lipid metabolism plays a crucial role in cancer progression,and long non-coding RNAs(lncRNAs)are emerging as key regulators in tumor biology.However,the prognostic and therapeutic implications of lipid metabolism-related lncRNAs in lung adenocarcinoma(LUAD)remain unclear.This study aimed to identify lipid metabolism-associated lncRNAs,construct a prognostic model,and explore their clinical relevance in LUAD.Methods Transcriptomic and clinical data from LUAD patients were obtained from The Cancer Genome Atlas(TCGA).Co-expression networks,functional enrichment(GO/KEGG),and survival analyses(univariate/multivariate Cox regression,LASSO)were used to identify prognostic lncRNAs.A risk prediction model was developed and validated using tumor mutation burden(TMB),immune microenvironment analysis,and drug sensitivity profiling.Mendelian randomization(MR)and Bayesian weighting were employed to assess causal relationships between lipid metabolism pathways and LUAD.Results Three lipid metabolism-related lncRNAs—LINC00862 and AC125807.2(risk factors)and LINC01447(protective factor)—were significantly associated with LUAD prognosis.The risk model stratified patients into high-and lowrisk groups with distinct sur-vival outcomes(p<0.001).High-risk patients exhibited elevated TMB and immune dysfunction but greater sensitivity to chemotherapy(e.g.,cisplatin,gemcitabine),while low-risk patients showed potential responsiveness to targeted therapies(e.g.,PAK1/GSK-3 inhibitors).MR analysis confirmed that normal lipid metabolism pathways(linoleic acid/fatty acid metabolism)reduce LUAD risk(IVW p<0.05).Conclusion This study identifies lipid metabolism-related lncRNAs as novel prognostic biomarkers in LUAD,with implications for risk stratification and personalized therapy.The findings highlight the interplay between lipid metabolism,immune regulation,and therapeutic response,offering a foundation for future clinical validation and targeted interventions. 展开更多
关键词 TCGA NSCLC Lipid metabolism Long non-coding RNA Immunotherapy Mendelian randomization analysis
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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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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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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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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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Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy 认领 引用
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作者 Cheng-Ye Tang Dong-Yong Tang +2 位作者 Ying-Qin Yang Yu-Bing Liang Hao Liang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第10期1905-1910,共6页
AIM:To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy(DR)utilizing a two-sample Mendelian randomization(MR)analysis.METHODS:The research data were obta... AIM:To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy(DR)utilizing a two-sample Mendelian randomization(MR)analysis.METHODS:The research data were obtained from summary statistics of genome-wide association studies(GWAS).Genetic loci closely related to cheese intake were extracted as instrumental variables(IVs),and DR was the outcome variable.The data were extracted from individuals of European ethnicity.The data of cheese intake consisted of 451486 samples with 9851867 single nucleotide polymorphisms(SNPs),while the DR data consisted of 206234 samples with 16380446 SNPs.Sixty-one genetic loci closely related to cheese intake were selected as IVs.MR analysis was performed by inverse-variance weighted(IVW)method and MR-Egger regression respectively.The causal relationship between cheese intake and DR was evaluated using odds ratios(ORs)and 95%confidence intervals(CIs).Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test.RESULTS:The P value of the IVW method was less than 0.05,indicating a significant negative correlation between cheese intake and DR.MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022,and a P-value of 0.634,indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors.Besides,heterogeneity tests confirmed the absence of heterogeneity,and the“leave-one-out”sensitivity analysis demonstrated that the results were stable.CONCLUSION:Cheese intake is causally negatively correlated with the occurrence of DR,and cheese intake could reduce the risk of DR. 展开更多
关键词 cheese intake diabetic retinopathy Mendelian randomization analysis
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Diabetes mellitus and prostate cancer risk:A mendelian randomization analysis 认领 引用 被引量：2
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作者 Jian-Xu Yuan Qing Jiang Sheng-Jie Yu 《World Journal of Diabetes》 SCIE 2023年第12期1839-1848,共10页
BACKGROUND Some studies have directed towards an association between diabetes mellitus(DM)and prostate cancer(PCa);however,this specific relationship remains inconclusive.In recent years,Mendelian randomization(MR)has... BACKGROUND Some studies have directed towards an association between diabetes mellitus(DM)and prostate cancer(PCa);however,this specific relationship remains inconclusive.In recent years,Mendelian randomization(MR)has become a widely used analytical method for inferring epidemiological causes.AIM To investigated the potential relationship between DM and PCa using MR.METHODS We downloaded relevant data on"diabetes"and"PCa"from the IEU OpenGWAS project database,performed three different methods to conduct MR,and carried out sensitivity analysis for verification.RESULTS The results indicated that DM was an independent risk factor for PCa.The odds ratio(OR)values obtained using the inverse variance weighted method in this study were as follows:OR=1.018(95%confidence interval:1.004-1.032),P=0.014.CONCLUSION We found that DM could increase the incidence rate of PCa. 展开更多
关键词 Prostate cancer Diabetes mellitus Mendelian randomization analysis Risk factors Genome-wide association study
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Sensitivity analysis for causal mediation analysis with Mendelian randomization 认领 引用
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作者 Zhiya Chen Yuxi Chen Hong Zhang 《中国科学技术大学学报》 CAS CSCD 北大核心 2024年第12期22-32,49,I0004,I0008,I0009,共11页
Mendelian randomization(MR)is widely used in causal mediation analysis to control unmeasured confounding effects,which is valid under some strong assumptions.It is thus of great interest to assess the impact of violat... Mendelian randomization(MR)is widely used in causal mediation analysis to control unmeasured confounding effects,which is valid under some strong assumptions.It is thus of great interest to assess the impact of violations of these MR assumptions through sensitivity analysis.Sensitivity analyses have been conducted for simple MR-based causal average effect analyses,but they are not available for MR-based mediation analysis studies,and we aim to fill this gap in this paper.We propose to use two sensitivity parameters to quantify the effect due to the deviation of the IV assumptions.With these two sensitivity parameters,we derive consistent indirect causal effect estimators and establish their asymptotic propersties.Our theoretical results can be used in MR-based mediation analysis to study the impact of violations of MR as-sumptions.The finite sample performance of the proposed method is illustrated through simulation studies,sensitivity ana-lysis,and application to a real genome-wide association study. 展开更多
关键词 Mendelian randomization mediation analysis sensitivity analysis summary data
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Future risk of falls induced by ankle-foot sprains history:An observational and mendelian randomization study 认领 引用
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作者 Xiao'ao Xue Weichu Tao +9 位作者 Qianru Li Yi Li Yiran Wang Le Yu Xicheng Gu Tian Xia Rong Lu Ru Wang He Wang Yinghui Hua 《Sports Medicine and Health Science》 CSCD 2025年第3期214-223,共10页
Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association ... Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.Methods:UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted.Then,the two-sample Mendelian randomization(MR)analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship.Finally,genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.Results:Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates(odd ratio[OR]ranged from 1.632 to 1.658).Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls(OR=1.036)and a lower fractional anisotropy of superior cerebellar peduncle(SCP)(left,β=0.052;right,β=0.053).A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls(β=0.003).Conclusion:The history of ankle-foot sprains is associated with a slightly increased risk of falls.These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries. 展开更多
关键词 Leg injuries Accidental falls Postural balance Mendelian randomization analysis UK biobank FinnGen
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Causal relationships among gut microbiota, blood metabolites, and urticaria in East Asians: A Mendelian randomization study 认领 引用
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作者 HUANG Yuzhou WANG Dan LU Jianyun 《中南大学学报（医学版）》 CAS CSCD 北大核心 2025年第9期1590-1601,共12页
Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the caus... Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation. 展开更多
关键词 urticaria gut microbiota blood metabolites Mendelian randomization mediation analysis
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Causal associations of plasma proteins with lung squamous cell carcinoma risk:a proteome-wide Mendelian randomization and colocalization analysis 认领 引用
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作者 Qing Wang Xiaofei Xue +3 位作者 Xinyu Ling Yukuan Lang Suyu Wang Gang Liu 《Clinical Cancer Bulletin》 2024年第1期64-73,共10页
Background Lung squamous cell carcinoma(LUSC)is a major subtype of non-small cell lung cancer with a high mortality rate.Identifying causal plasma proteins associated with LUSC could provide new insights into the path... Background Lung squamous cell carcinoma(LUSC)is a major subtype of non-small cell lung cancer with a high mortality rate.Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets.This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization(MR)and colocalization analyses.Methods Proteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics.Summary-level data for LUSC were obtained from the ILCCO Consortium,the FinnGen study,and a separate GWAS study.A total of 1,046 shared protein quantitative trait loci(pQTLs)were analyzed.Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations.Results MR analysis identified six plasma proteins associated with LUSC risk:HSPA1L,PCSK7,POLI,SPINK2,TCL1A,and VARS.HSPA1L(OR=0.47;95%CI:0.34–0.65;P=4.89×10–6),SPINK2(OR=0.68;95%CI:0.58–0.80;P=3.17×10–6),and VARS(OR=0.44;95%CI:0.31–0.63;P=5.94×10–6)were associated with a decreased risk of LUSC.Conversely,PCSK7(OR=1.37;95%CI:1.21–1.56;P=1.40×10–6),POLI(OR=4.50;95%CI:2.25–9.00;P=2.13×10–5),and TCL1A(OR=1.72;95%CI:1.34–2.21;P=1.89×10–5)were associated with an increased risk.The SMR analysis and HEIDI test confirmed the robustness of these associations.HSPA1L,SPINK2,and VARS showed significant inverse associations,with strong colocalization evidence for TCL1A(PPH4=0.817).Conclusions This study identified six plasma proteins potentially causal for LUSC risk.HSPA1L,SPINK2,and VARS are associated with decreased risk,while PCSK7,POLI,and TCL1A are linked to increased risk.These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention. 展开更多
关键词 Lung squamous cell carcinoma Proteome-wide Mendelian randomization Plasma proteins Genetic instruments Colocalization analysis HSPA1L PCSK7 POLI SPINK2 TCL1A VARS
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Causal relationship between multiple types of food intake and myopia:a Mendelian randomization study 认领 引用
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作者 Sha-Sha Zhang Jiao-Jiao Liang +4 位作者 Yun Feng Xia Hong Yi-Jia Zhao Ling Chen Ping Lin 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2025年第9期1718-1729,共12页
AIM:To investigate the causal relationship between dietary intake and myopia using Mendelian randomization(MR)analysis.METHODS:Genome-wide association study(GWAS)data from the IEU Open GWAS database were utilized to e... AIM:To investigate the causal relationship between dietary intake and myopia using Mendelian randomization(MR)analysis.METHODS:Genome-wide association study(GWAS)data from the IEU Open GWAS database were utilized to examine associations between myopia and various dietary factors.MR analysis,incorporating both univariable and multivariable approaches,assessed the impact of food intake on myopia risk through five analytical methods,with inverse variance weighted(IVW)serving as the primary reference.Sensitivity analyses,including heterogeneity assessment,horizontal pleiotropy evaluation,and leave-oneout analysis,were conducted to validate the MR findings.RESULTS:Univariable MR analysis identified a causal link between food intake and myopia.Consumption of breaded fish,canned soup,sweet biscuits,and certain fruits correlated with a lower risk of myopia,whereas intake of low-calorie hot chocolate and cereal was associated with an increased risk.Multivariable MR analysis further confirmed that breaded fish consumption exerted a direct protective effect against myopia,particularly when consumed alongside other dietary components.These findings highlight the intricate interplay between specific dietary factors and myopia development,offering valuable insights for further research.CONCLUSION:MR analysis provides evidence supporting a potential causal relationship between breaded fish intake and myopia,underscoring its relevance in targeted myopia prevention strategies. 展开更多
关键词 myopia genome-wide association study food intakes univariable Mendelian randomization analysis multivariable Mendelian randomization analysis
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Causal relationship between feelings and cognitive decline:An univariable and multivariable Mendelian randomization study 认领 引用
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作者 Juan Liu Lin Liu +4 位作者 Yi-Xin Hu Jian-Hua Li Xiao Zou Hao-Yun Zhang Li Fan 《World Journal of Psychiatry》 SCIE 2024年第3期421-433,共13页
BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and co... BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(ORMVMR=0.39,95%CI:0.17-0.90,PMVMR=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(ORMVMR=1.42,95%CI:0.43-4.74,PMVMR=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in identifying the effect.Notably,this study did not demonstrate any significant impact of guilty feelings,nervous feelings,miserableness,or loneliness/isolation on cognition.Due to a limited number of instrumental variables for happiness,this study was unable to analyze the relationship between happiness and cognition.CONCLUSION This MR study finds that sensitivity/hurt feelings are associated with cognitive decline,while the link between worrier/anxious feelings and cognition remains inconclusive.Insufficient evidence supports direct associations between happiness,guilty feelings,nervous feelings,miserableness,loneliness/isolation,and cognition. 展开更多
关键词 Mendelian randomization analysis Feelings Cognition Intelligence
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Causal association of obesity-related anthropometric traits with myopia and the mediating role of educational attainment:a Mendelian randomization study 认领 引用 被引量：3
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作者 Yi Lu Can-Can Zhang +4 位作者 Run-Ting Ma Yuan-Jing Li Wen-Ping Li Die-Wen-Jie Hu Lian-Hong Zhou 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第11期2082-2092,共11页
AIM:To study the causal relationship between obesityrelated anthropometric traits and myopia and the mediating role of educational attainment(EA).METHODS:Univariable Mendelian randomization(UVMR)was performed to evalu... AIM:To study the causal relationship between obesityrelated anthropometric traits and myopia and the mediating role of educational attainment(EA).METHODS:Univariable Mendelian randomization(UVMR)was performed to evaluate the causal association between body mass index(BMI),height,waist-hip ratio(WHR,adjusted for BMI),and mean spherical equivalent(MSE).BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization(MVMR)to explore the roles of different BMI components in the causal relationship between BMI and MSE.A mediation analysis based on two-step Mendelian randomization(MR)was carried out.Specifically,UVMR was conducted to estimate the causal effect of BMI on EA.The direct effect of EA on MSE was estimated from MVMR.The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method.Expression quantitative trait loci(eQTL)-MR,reverse MR,and Linkage Disequilibrium Score Regression(LDSC)were performed to assess the robustness.RESULTS:Genetically predicted higher BMI had a positive total effect on MSE(βIVW=0.26 D,95%CI=0.14 to 0.37 D,P<0.001),whereas there was no significant association between height,WHR,and MSE.Fat mass was found to play a significant role in the effect of body mass on MSE(βIVW=0.50 D,95%CI=0.21 to 0.78 D,P=0.001),but there was no significant association between fat-free mass and MSE.The causal effect of BMI on EA was-0.14(95%CI=-0.16 to-0.11,P<0.001),and the direct effect of EA on MSE was-0.63 D(95%CI=-0.81 to-0.44 D,P<0.001).The mediating effect of EA in the BMI-EA-MSE model was 0.09 D(95%CI=0.06 to 0.12 D),with a mediation proportion of 33%(95%CI=22.1%to 44.6%).No reverse causal associations were detected except for BMI on EA.The results of eQTL-MR and LDSC were consistent with each MR analysis.CONCLUSION:Genetically predicted higher BMI decreases the degree of myopia with a 33%mediation proportion by EA,and fat mass provides a dominant protective role in body mass-myopia.As a supplement to previous observational studies,it provides strong evidence for the relationship between anthropometric traits and refractive errors and offers a theoretical basis for future measures to prevent and control myopia. 展开更多
关键词 myopia anthropometric traits educational attainment mediation analysis Mendelian randomization
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Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis:A Bidirectional Mendelian Randomization Study 认领 引用
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作者 Hao Lv Ge Zhang +3 位作者 Zhi-Mu Hu Qing-Song Chu Jiu-Xiang Wang Ting Jiang 《Chinese Medical Sciences Journal》 CAS CSCD 2024年第3期185-192,共8页
Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wid... Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis. 展开更多
关键词 osteoporosis plasma metabolites mendelian randomization bidirectional analysis
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Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study 认领 引用 被引量：2
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作者 Wei-Hao Chai Yan Ma +3 位作者 Jia-Jia Li Fei Guo Yi-Zhan Wu Jiang-Wei Liu 《World Journal of Clinical Cases》 SCIE 2024年第17期3094-3104,共11页
BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I... BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families. 展开更多
关键词 Irritable bowel syndrome Immunophenotypes Causality Brain-gut axis Mendelian randomization Sensitivity analysis
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Association of education with cholelithiasis and mediating effects of cardiometabolic factors:A Mendelian randomization study 认领 引用
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作者 Chang-Lei Li Yu-Kun Liu +1 位作者 Ying-Ying Lan Zu-Sen Wang 《World Journal of Clinical Cases》 SCIE 2024年第20期4272-4288,共17页
BACKGROUND Education,cognition,and intelligence are associated with cholelithiasis occurrence,yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationsh... BACKGROUND Education,cognition,and intelligence are associated with cholelithiasis occurrence,yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated.AIM To explore the causal associations between education,cognition,and intelligence and cholelithiasis,and the cardiometabolic risk factors that mediate the associations.METHODS Applying genome-wide association study summary statistics of primarily European individuals,we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education,intelligence,and cognition on cholelithiasis and cholecystitis(FinnGen study,37041 and 11632 patients,respectively;n=486484 participants)and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis.RESULTS Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education,cognition,or intelligence were not independently associated with cholelithiasis and cholecystitis;when adjusted for cholelithiasis,higher education still presented an inverse effect on cholecystitis[odds ratio:0.292(95%CI:0.171-0.501)],which could not be induced by cognition or intelligence.Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis,including body mass index(20.84%),body fat percentage(40.3%),waist circumference(44.4%),waist-to-hip ratio(32.9%),and time spent watching television(41.6%),while time spent watching television was also a mediator from cognition(20.4%)and intelligence to cholelithiasis(28.4%).All results were robust to sensitivity analyses.CONCLUSION Education,cognition,and intelligence all play crucial roles in the development of cholelithiasis,and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure. 展开更多
关键词 Cholelithiasis Mendelian randomization Mediation analysis Education attainment Cardiometabolic risk factors Cognition Intelligence
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Functional investigation and two-sample Mendelian randomization study of primary biliary cholangitis hub genes 认领 引用
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作者 Yun-Chuan Yang Xiang Ma +5 位作者 Chi Zhou Nan Xu Ding Ding Zhong-Zheng Ma Lei Zhou Pei-Yuan Cui 《World Journal of Clinical Cases》 SCIE 2024年第30期6391-6406,共16页
BACKGROUND The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis(PBC)and finding relevant biomarkers for diagnosis and therapeutic e... BACKGROUND The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis(PBC)and finding relevant biomarkers for diagnosis and therapeutic evaluation.AIM To determine PBC-associated hub genes and assess their clinical utility for disease prediction.METHODS PBC expression data were obtained from the Gene Expression Omnibus database.Overlapping genes from differential expression analysis and weighted gene coexpression network analysis(WGCNA)were identified as key genes for PBC.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed to explore the potential roles of key genes.Hub genes were identified in protein-protein interaction(PPI)networks using the Degree algorithm in Cytoscape software.The relationship between hub genes and immune cells was investigated.Finally,a Mendelian randomization study was conducted to determine the causal effects of hub genes on PBC.RESULTS We identified 71 overlapping key genes using differential expression analysis and WGCNA.These genes were primarily enriched in pathways related to cytokinecytokine receptor interaction,and Th1,Th2,and Th17 cell differentiation.We utilized Cytoscape software and identified five hub genes(CD247,IL10,CCL5,CCL3,and STAT3)in PPI networks.These hub genes showed a strong correlation with immune cell infiltration in PBC.However,inverse variance weighting analysis did not indicate the causal effects of hub genes on PBC risk.CONCLUSION Hub genes can potentially serve as valuable biomarkers for PBC prediction and treatment,thereby offering significant clinical utility. 展开更多
关键词 Primary biliary cholangitis Weighted gene co-expression network analysis Hub genes Mendelian randomization Bioinformatic analysis
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