BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS...BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS:Data were summarized using genome-wide association studies (GWAS).Twosample MR analyses were performed using the inverse variance weighting (IVW) method,the weighted median method,and the MR-Egger analysis.Heterogeneity test and sensitivity analysis were performed using Cochran’s Q test and the leave-one-out method,respectively.The Steiger test was used to detect reverse causality.Bayesian model-averaged MR was used to identify the most influential risk factors.RESULTS:A total of 13 GWAS data were collected for BMI,body weight and WC.IVW analyses showed a positive correlation of body weight,BMI,and WC with CA (all OR>1 and P<0.05),with MR-Egger and weighted median methods confirming the IVW findings.No horizontal pleiotropy or heterogeneity was observed.Sensitivity analysis indicated that no single nucleotide polymorphism(SNP) caused significant changes in overall causality.Bayesian model-averaged MR was also used to rank causality based on marginal inclusion probability (MIP),and the corresponding modelaveraged causal estimate (MACE) were confirmed,which indicated that WC (GWAS ID:ukb-b-9405)was the highest-ranked risk factor (MIP=0.119,MACE=0.011);its posterior probability was 0.057.A total of 14 sex-specific GWAS data on weight,BMI,and WC were analyzed in relationship with CA,and the MR results showed no significant effects of sex-specific factors.CONCLUSION:Body weight,BMI,and WC are causally associated with an increased risk of CA,with WC identified as the most important risk factor.展开更多
Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observati...Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observational studies.The objective of this study was to explore the causal association between PM_(2.5)exposure,its absorbance,and IBD.Methods We assessed the association of PM_(2.5)and PM_(2.5)absorbance with the two primary forms of IBD(Crohn’s disease[CD]and ulcerative colitis[UC])using Mendelian randomization(MR)to explore the causal relationship.We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study.Single-nucleotide polymorphisms linked with PM_(2.5)concentrations or their absorbance were used as instrumental variables(IVs).We used inverse variance weighting(IVW)as the primary analytical approach and four other standard methods as supplementary analyses for quality control.Results The results of MR demonstrated that PM_(2.5)had an adverse influence on UC risk(odds ratio[OR]=1.010;95%confidence interval[CI]=1.001–1.019,P=0.020).Meanwhile,the results of IVW showed that PM_(2.5)absorbance was also causally associated with UC(OR=1.012;95%CI=1.004–1.019,P=0.002).We observed no causal relationship between PM_(2.5),PM_(2.5)absorbance,and CD.The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy,ensuring the reliability of MR results.Conclusion Based on two-sample MR analyses,there are potential positive causal relationships between PM_(2.5),PM_(2.5)absorbance,and UC.展开更多
Background:Previous studies have suggested that allergic diseases and cancer development are inversely correlated.However,the association between allergic disease biomarkers and the risk of hepatocellular carci-noma(H...Background:Previous studies have suggested that allergic diseases and cancer development are inversely correlated.However,the association between allergic disease biomarkers and the risk of hepatocellular carci-noma(HCC)has not been thoroughly investigated.Objective:This study aimed to investigate the association between biomarkers of allergic diseases and HCC by performing a Mendelian randomization study.Methods:An analysis was performed on the following data from a genome-wide association study(GWAS):eosinophil count(n=172,275 samples),basophil count(n=11,502),IL-4(n=8124),IL-5(n=3364),IL-10(n=7681),IL-13(n=3557),tIgE(n=1000),TGF-β(n=982),and HCC cases(n=197,611).The inverse-variance weighted(IVW)approach was used for the principal analysis,complemented by MR-Egger,weighted median,simple mode,and weighted mode analyses.Results:The results of the IVW method indicated that genetically predicted eosinophils were significantly asso-ciated with a decreased risk of HCC(odds ratio[OR]=0.80;95%CI:0.65-0.97;p=0.03).The results of the IVW analysis revealed a significant association between elevated levels of IL-4 and decreased risk of HCC(OR=0.64;95%CI:0.43-0.95;p=0.03).Furthermore,all p-values calculated in the MR-Egger intercept test were greater than 0.05,indicating the absence of instrumental variables in horizontal pleiotropy.Conclusion:Eosinophil and IL-4 levels were associated with a decreased risk of HCC,suggesting a possible pro-tective effect of allergic diseases against the risk of HCC.These findings provide new insights into the etiology,diagnosis,and treatment of HCC.展开更多
Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sam...Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.展开更多
Background:Both eczema and tumor are associated with immune disorders.Although several investigations have observed the rela-tionship between eczema and certain cancers,evidence for causality is lacking.Methods:We con...Background:Both eczema and tumor are associated with immune disorders.Although several investigations have observed the rela-tionship between eczema and certain cancers,evidence for causality is lacking.Methods:We conducted a two-sample Mendelian randomization(MR)study to examine and explore the genetic association between eczema and pan-cancers.Upon satisfying the three core assumptions of MR,we analyzed the causality between eczema and 15 site-specific cancers utilizing an inverse variance weighted method.We verified the results through a series of sensitivity and reverse direction analyses.The exposure and outcome datasets were substituted from the FinnGen and genome-wide association studies catalog data-bases.A meta-analysis on primary and validation analyses was performed to combine the estimates of MR study.Results:Based on the MR analysis results,eczema was associated with an increased risk of lung cancer(odds ratio[OR]=1.0427,95%confidence interval[CI]=1.0082–1.0783,P=0.0148)and brain cancer(OR=1.0285,95%CI=1.0120–1.0452,P=0.0007)and de-creased risk of colorectal cancer(OR=0.9324,95%CI=0.8774–0.9909,P=0.0242)and malignant neoplasm of the kidney(OR=0.9323,95%CI=0.8834–0.9839,P=0.0108).The sensitivity analysis indicated that the results were stable and reliable,and the reverse MR analyses demonstrated no causation between the cancers of interest and eczema.Conclusions:Our results identified eczema as a genetic risk factor for lung and brain cancer and a protective factor for colorectal cancer and malignant neoplasm of the kidney.No connection was observed between eczema and other cancers.Further evidence from epide-miological and mechanistic studies is needed to elucidate these findings in detail.展开更多
Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In...Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.展开更多
AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcer...AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.展开更多
BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship bet...BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.展开更多
BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To asses...BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.展开更多
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
Background:The relationship between tea intake(TI)and sleep disorders(SDs)has been a topic of interest for some time,but there remains a lack of data showing a causal relationship.We aimed to use a two-sample Mendelia...Background:The relationship between tea intake(TI)and sleep disorders(SDs)has been a topic of interest for some time,but there remains a lack of data showing a causal relationship.We aimed to use a two-sample Mendelian randomization study to determine whether there is a causal link between TI and SDs.Methods:We collected data regarding TI,with a focus on green tea intake(GTI),herbal tea intake(HTI),and rooibos tea intake(RTI);and data regarding SDs and insomnia from genome-wide association studies.We analyzed these data using an inverse variance-weighted two-sample Mendelian randomization study,by means of the TwoSampleMR package in R4.2.3 software.Results:We found no genetic causal relationships of TI,GTI,HTI,or RTI with insomnia.The odds ratios(ORs)for these relationships were as follows:TI:OR=0.61,95%confidence interval(CI):0.29–1.28;GTI:OR=1.04,95%CI:0.95–1.14;HTI:OR=0.98,95%CI:0.82–1.17;and RTI:OR=1.04,95%CI:0.99–1.09.In addition,there were no genetic causal relationships of TI,GTI,HTI,or RTI with SDs.The OR values for these relationships were as follows:TI:OR=0.6,95%CI:0.34–1.06;GTI:OR=1,95%CI:0.93–1.07;HTI:OR=0.89,95%CI:0.66–1.2;and RTI:OR=1.02,95%CI:0.98–1.06.Conclusion:We found no causal relationships of TI with SDs or insomnia,irrespective of the type of tea consumed.However,additional Mendelian randomization studies are required to further explore the relationships of the timing and quantity of tea consumption with SDs and insomnia.展开更多
Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentiall...Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentially lowering CA incidence.This study aims to employ Mendelian Randomization(MR)methodology to explore the genetic causality between TI and CA.Methods:We collected Genome-wide association study(GWAS)data for CA,TI,Green tea intake(GTI),Herbal tea intake(HTI),and Rooibos tea intake(RTI).The MR analysis employed the TwoSampleMR package and utilized the inverse variance-weighted(IVW)method.Results:The findings suggest no genetic causal relationship between TI and CA(IVW:OR=1.10,95%CI:0.59–2.05,P=0.772).Similarly,there is no genetic causal association between GTI and CA(IVW:OR=1.07,95%CI:0.91–1.26,P=0.388),HTI and CA(IVW:OR=1.00,95%CI:0.89–1.13,P=0.943),or RTI and CA(IVW:OR=1.02,95%CI:0.96–1.09,P=0.472).Conclusion:There is no genetic causal relationship between TI and CA,and the different types of tea do not change this result.Further MR analysis is needed to investigate whether there is a potential genetic causal association between the quantity of TI and CA.展开更多
Background:Previous studies have suggested a potential risk-reducing effect of tea intake(TI)on diabetes.However,the specific impacts of TI on different types of diabetes and its underlying mechanisms remain unclear.T...Background:Previous studies have suggested a potential risk-reducing effect of tea intake(TI)on diabetes.However,the specific impacts of TI on different types of diabetes and its underlying mechanisms remain unclear.To further explore this topic,we conducted a comprehensive investigation to assess the causal relationship between TI and various types of diabetes,as well as its effects on blood glucose(Glu)and glycated hemoglobin(HbA1).Methods:We collected genome-wide association study data for TI,diabetes,type 1 diabetes(T1D),type 2 diabetes(T2D),Glu,HbA1,green tea intake,herbal tea intake,and Rooibos tea intake from the IEU database.Subsequently,we performed two-sample Mendelian randomization analysis using the TwoSampleMR package.Results:Our analysis revealed no evidence of a causal relationship between TI and the incidence of diabetes,T1D,blood Glu,HbA1c,or T2D.Similarly,no genetic causal relationship was found between green tea intake and diabetes,T1D,T2D,Glu,or HbA1c.The same applied to herbal tea intake and Rooibos tea intake,as there was no genetic causal link with diabetes,T1D,T2D,Glu,or HbA1c.Conclusion:Based on our findings,there is no indication of a causal relationship between TI and the incidence of all types of diabetes,regardless of the specific tea type.However,to comprehensively understand the potential effects of TI on diabetes incidence,including the quantity and timing of intake,further evaluation through additional Mendelian randomization studies is warranted.展开更多
Dear Editor,Observational studies in epidemiology have identified a correlation between hypothyroidism and cholelithiasis[1–2].However,the causal relationship between the two diseases remains unclear.To investigate t...Dear Editor,Observational studies in epidemiology have identified a correlation between hypothyroidism and cholelithiasis[1–2].However,the causal relationship between the two diseases remains unclear.To investigate the potential causal relationship,we employed a two-sample bidirectional Mendelian randomization(MR)analysis.展开更多
Objective The association between myopia and diabetic retinopathy(DR)is unclear,with inconsistent results reported,and whether the association represents causality remains unknown.This study aimed to investigate the c...Objective The association between myopia and diabetic retinopathy(DR)is unclear,with inconsistent results reported,and whether the association represents causality remains unknown.This study aimed to investigate the causal associations of genetically determined myopia with DR,and further explore specific mechanisms.Methods We conducted two-sample mendelian randomization(MR)analyses of any myopia and high myopia on six DR phenotypes,including any DR,background DR,severe background DR,proliferative DR(PDR),diabetic maculopathy and unspecific DR in the primary study.Mechanism exploration of spherical equivalent refraction(SER),corneal curvature(CC)and axial length(AL)on any DR was carried out subsequently.Single-nucleotide polymorphisms(SNPs),used as genetic instruments,were derived from UK Biobank,Genetic Epidemiology Research on Adult Health and Aging cohort(GERA)and FinnGen.The inverse variance weighted(IVW)method was mainly used to assess the causality,and was complemented with sensitivity analyses and causality direction analyses.Results Using SNPs that have excluded possible confounders,we discovered suggestive and positive causal associations of any myopia with any DR(IVW:odds ratio[OR]=1.133,95%confidence interval[95%CI]:1.070-1.201,P=1.91×10^(-5))and PDR(IVW:OR=1.182,95%CI:1.088-1.285,P=8.31×10^(-5)).Similar but more significant associations were found of high myopia with any DR and PDR(IVW:OR=1.107,95%CI:1.051-1.166,P=1.39×10^(-4);OR=1.163,95%CI:1.088-1.244,P=8.76×10^(-6),respectively).Further mechanism analyses found only AL,rather than SER or CC,was strongly and significantly associated with any DR.These associations were robust in sensitivity analyses and causality direction analyses.Conclusions We found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR,which might be related with AL,indicating the significance of myopia control for preventing DR development and progression.展开更多
Biliary tract cancer(BTC)seriously endangers human health.Recently,with the increasing development of therapeutic strategies,exploration of novel targeted and prognostic biomarkers has become a promising field of stud...Biliary tract cancer(BTC)seriously endangers human health.Recently,with the increasing development of therapeutic strategies,exploration of novel targeted and prognostic biomarkers has become a promising field of study(1).Newly developed biomarker signatures by Zhu et al.at the Biomarker Research significantly provide the potential prognostic and predictive values of the gut microbiome and metabolites for clinical outcomes in the management of patients with BTC(2).展开更多
Background and Objectives:Previous studies have reported there were associations between ovarian function and dietary factors,metabolic factors and gut microbiota.However,it is unclear whether causal associations exis...Background and Objectives:Previous studies have reported there were associations between ovarian function and dietary factors,metabolic factors and gut microbiota.However,it is unclear whether causal associations exist.We aimed to explore the causal relationship of these factors with risk of primary ovarian failure(POF).Methods and Study Design:Two-sample Mendelian randomization(MR)analysis was performed to genetically predict the causal effects of dietary and metabolic factors and gut microbiota on POF.The inverse variance weighted(IVW)method was used as the primary statistical method.A series of sensitivity analyses,including weighted median,MR-Egger,simple mode,weighted mode methods,and leave-one-out analysis,were conducted to assess the robustness of the MR analysis results.Results:IVW analysis revealed that cigarettes smoked per day,coffee intake and cooked vegetable intake were not causally correlated with POF at the genetic level.However,POF were associated with fresh fruit intake,BMI,Eubacterium(hallii group),Eubacterium(ventriosum group),Ad lercreutzia,Intestinibacter,Lachnospiraceae(UCG008),and Terrisporobacter.These findings were robust ac cording to extensive sensitivity analyses.Conclusions:This study identified several dietary factors,metabolic factors and gut microbiota taxa that may be causally implicated in POF,potentially offering new therapeutic tar gets.展开更多
Objective:To investigate the causal relationship between blood metabolite levels and the occurrence of prostate cancer by using two-sample Mendelian randomization method.Methods:Pooled data from public databases for g...Objective:To investigate the causal relationship between blood metabolite levels and the occurrence of prostate cancer by using two-sample Mendelian randomization method.Methods:Pooled data from public databases for genome-wide association analyses of blood metabolites and prostate cancer were selected,and inverse variance weighting(IVW)was used as the primary method for estimating the causal effects,while heterogeneity tests,gene multiplicity tests and sensitivity analyses were performed to assess the stability and reliability of the results.Results:A total of six known metabolites were found to potentially increase the risk of prostate cancer development(P<0.05),namely fructose,allantoin,5-hydroxytryptophan,potassium ketoisocaproate,glycyltryptophan,and 1-heptadecanoyl-glycerol-3-phosphorylcholine,with no heterogeneity or genetic pleiotropy found.Conclusion:Six known blood metabolites may be potential risk factors for prostate cancer development in European populations.展开更多
Background Studies on the association between oxidative stress and epilepsy have yielded varied results.In this study,we aimed to investigate the causal relationship between oxidative stress markers and epilepsy.Metho...Background Studies on the association between oxidative stress and epilepsy have yielded varied results.In this study,we aimed to investigate the causal relationship between oxidative stress markers and epilepsy.Methods A bidirectional two-sample Mendelian randomization(MR)study was performed based on publicly available statistics from genome-wide association studies.To explore the causal efects,single nucleotide polymorphisms were selected as instrumental variables.Inverse-variance weighted method was performed for primary analysis,supplemented by weighted median,MR-Egger,simple mode,and weighted mode.Furthermore,sensitivity analyses were performed to detect heterogeneity and pleiotropy.Results Our results showed that part of the oxidative stress biomarkers are associated with epilepsy and its subtypes.Zinc is associated with increased risk of epilepsy and generalized epilepsy(odds ratio[OR]=1.064 and 1.125,respectively).Glutathione transferase is associated with increased risk of generalized epilepsy(OR=1.055),while albumin is associated with decreased risk of generalized epilepsy(OR=0.723).Inverse MR analysis revealed that epilepsy is associated with increased levels of uric acid and total bilirubin(beta=1.266 and 0.081,respectively),as well as decreased zinc level(beta=−0.278).Furthermore,generalized epilepsy is associated with decreased ascorbate and retinol levels(beta=−0.029 and−0.038,respectively).Conclusions Our study presented novel evidence of potential causal relationships between oxidative stress and epilepsy,suggesting potential therapeutic targets for epilepsy.展开更多
基金This study is supported by the National Natural Science Foundation of China (No. 82072127)。
文摘BACKGROUND:This study aims to explore the causal relationship of body weight,body mass index(BMI),and waist circumference (WC) with the risk of cardiac arrest (CA) using two-sample Mendelian randomization (MR).METHODS:Data were summarized using genome-wide association studies (GWAS).Twosample MR analyses were performed using the inverse variance weighting (IVW) method,the weighted median method,and the MR-Egger analysis.Heterogeneity test and sensitivity analysis were performed using Cochran’s Q test and the leave-one-out method,respectively.The Steiger test was used to detect reverse causality.Bayesian model-averaged MR was used to identify the most influential risk factors.RESULTS:A total of 13 GWAS data were collected for BMI,body weight and WC.IVW analyses showed a positive correlation of body weight,BMI,and WC with CA (all OR>1 and P<0.05),with MR-Egger and weighted median methods confirming the IVW findings.No horizontal pleiotropy or heterogeneity was observed.Sensitivity analysis indicated that no single nucleotide polymorphism(SNP) caused significant changes in overall causality.Bayesian model-averaged MR was also used to rank causality based on marginal inclusion probability (MIP),and the corresponding modelaveraged causal estimate (MACE) were confirmed,which indicated that WC (GWAS ID:ukb-b-9405)was the highest-ranked risk factor (MIP=0.119,MACE=0.011);its posterior probability was 0.057.A total of 14 sex-specific GWAS data on weight,BMI,and WC were analyzed in relationship with CA,and the MR results showed no significant effects of sex-specific factors.CONCLUSION:Body weight,BMI,and WC are causally associated with an increased risk of CA,with WC identified as the most important risk factor.
基金supported by the National Natural Science Foundation of China(No.82303169)the Key Research and Development Program of Shaanxi(No.2021ZDLSF02-06).
文摘Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observational studies.The objective of this study was to explore the causal association between PM_(2.5)exposure,its absorbance,and IBD.Methods We assessed the association of PM_(2.5)and PM_(2.5)absorbance with the two primary forms of IBD(Crohn’s disease[CD]and ulcerative colitis[UC])using Mendelian randomization(MR)to explore the causal relationship.We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study.Single-nucleotide polymorphisms linked with PM_(2.5)concentrations or their absorbance were used as instrumental variables(IVs).We used inverse variance weighting(IVW)as the primary analytical approach and four other standard methods as supplementary analyses for quality control.Results The results of MR demonstrated that PM_(2.5)had an adverse influence on UC risk(odds ratio[OR]=1.010;95%confidence interval[CI]=1.001–1.019,P=0.020).Meanwhile,the results of IVW showed that PM_(2.5)absorbance was also causally associated with UC(OR=1.012;95%CI=1.004–1.019,P=0.002).We observed no causal relationship between PM_(2.5),PM_(2.5)absorbance,and CD.The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy,ensuring the reliability of MR results.Conclusion Based on two-sample MR analyses,there are potential positive causal relationships between PM_(2.5),PM_(2.5)absorbance,and UC.
文摘Background:Previous studies have suggested that allergic diseases and cancer development are inversely correlated.However,the association between allergic disease biomarkers and the risk of hepatocellular carci-noma(HCC)has not been thoroughly investigated.Objective:This study aimed to investigate the association between biomarkers of allergic diseases and HCC by performing a Mendelian randomization study.Methods:An analysis was performed on the following data from a genome-wide association study(GWAS):eosinophil count(n=172,275 samples),basophil count(n=11,502),IL-4(n=8124),IL-5(n=3364),IL-10(n=7681),IL-13(n=3557),tIgE(n=1000),TGF-β(n=982),and HCC cases(n=197,611).The inverse-variance weighted(IVW)approach was used for the principal analysis,complemented by MR-Egger,weighted median,simple mode,and weighted mode analyses.Results:The results of the IVW method indicated that genetically predicted eosinophils were significantly asso-ciated with a decreased risk of HCC(odds ratio[OR]=0.80;95%CI:0.65-0.97;p=0.03).The results of the IVW analysis revealed a significant association between elevated levels of IL-4 and decreased risk of HCC(OR=0.64;95%CI:0.43-0.95;p=0.03).Furthermore,all p-values calculated in the MR-Egger intercept test were greater than 0.05,indicating the absence of instrumental variables in horizontal pleiotropy.Conclusion:Eosinophil and IL-4 levels were associated with a decreased risk of HCC,suggesting a possible pro-tective effect of allergic diseases against the risk of HCC.These findings provide new insights into the etiology,diagnosis,and treatment of HCC.
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
基金This work was supported by the National Natural Science Foundation (82273506,82273508)the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334),China。
文摘Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.
基金supported by the National Natural Science Foundation of China(no.82374229 and 82172839).
文摘Background:Both eczema and tumor are associated with immune disorders.Although several investigations have observed the rela-tionship between eczema and certain cancers,evidence for causality is lacking.Methods:We conducted a two-sample Mendelian randomization(MR)study to examine and explore the genetic association between eczema and pan-cancers.Upon satisfying the three core assumptions of MR,we analyzed the causality between eczema and 15 site-specific cancers utilizing an inverse variance weighted method.We verified the results through a series of sensitivity and reverse direction analyses.The exposure and outcome datasets were substituted from the FinnGen and genome-wide association studies catalog data-bases.A meta-analysis on primary and validation analyses was performed to combine the estimates of MR study.Results:Based on the MR analysis results,eczema was associated with an increased risk of lung cancer(odds ratio[OR]=1.0427,95%confidence interval[CI]=1.0082–1.0783,P=0.0148)and brain cancer(OR=1.0285,95%CI=1.0120–1.0452,P=0.0007)and de-creased risk of colorectal cancer(OR=0.9324,95%CI=0.8774–0.9909,P=0.0242)and malignant neoplasm of the kidney(OR=0.9323,95%CI=0.8834–0.9839,P=0.0108).The sensitivity analysis indicated that the results were stable and reliable,and the reverse MR analyses demonstrated no causation between the cancers of interest and eczema.Conclusions:Our results identified eczema as a genetic risk factor for lung and brain cancer and a protective factor for colorectal cancer and malignant neoplasm of the kidney.No connection was observed between eczema and other cancers.Further evidence from epide-miological and mechanistic studies is needed to elucidate these findings in detail.
文摘Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.
基金Supported by National Natural Science Foundation of China(No.82171085).
文摘AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.
文摘BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.
文摘BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.
基金Supported by School-Level Key Projects at Bengbu Medical College,No.2021byzd109。
文摘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.
基金supported by 2021 Construction project of key disciplines of Traditional Chinese Medicine(clinical)in Guangdong Province([2021]No.129)2020 Foshan City’s‘14th Five-Year’key specialized projects of traditional Chinese medicine(No.15).Foshan self-financing science and technology plan project(2320001009048).
文摘Background:The relationship between tea intake(TI)and sleep disorders(SDs)has been a topic of interest for some time,but there remains a lack of data showing a causal relationship.We aimed to use a two-sample Mendelian randomization study to determine whether there is a causal link between TI and SDs.Methods:We collected data regarding TI,with a focus on green tea intake(GTI),herbal tea intake(HTI),and rooibos tea intake(RTI);and data regarding SDs and insomnia from genome-wide association studies.We analyzed these data using an inverse variance-weighted two-sample Mendelian randomization study,by means of the TwoSampleMR package in R4.2.3 software.Results:We found no genetic causal relationships of TI,GTI,HTI,or RTI with insomnia.The odds ratios(ORs)for these relationships were as follows:TI:OR=0.61,95%confidence interval(CI):0.29–1.28;GTI:OR=1.04,95%CI:0.95–1.14;HTI:OR=0.98,95%CI:0.82–1.17;and RTI:OR=1.04,95%CI:0.99–1.09.In addition,there were no genetic causal relationships of TI,GTI,HTI,or RTI with SDs.The OR values for these relationships were as follows:TI:OR=0.6,95%CI:0.34–1.06;GTI:OR=1,95%CI:0.93–1.07;HTI:OR=0.89,95%CI:0.66–1.2;and RTI:OR=1.02,95%CI:0.98–1.06.Conclusion:We found no causal relationships of TI with SDs or insomnia,irrespective of the type of tea consumed.However,additional Mendelian randomization studies are required to further explore the relationships of the timing and quantity of tea consumption with SDs and insomnia.
文摘Background:Prior research has established a strong link between cerebral aneurysm(CA)occurrence and inflammation.Tea intake(TI)has been found to have anti-inflammatory properties through multiple mechanisms,potentially lowering CA incidence.This study aims to employ Mendelian Randomization(MR)methodology to explore the genetic causality between TI and CA.Methods:We collected Genome-wide association study(GWAS)data for CA,TI,Green tea intake(GTI),Herbal tea intake(HTI),and Rooibos tea intake(RTI).The MR analysis employed the TwoSampleMR package and utilized the inverse variance-weighted(IVW)method.Results:The findings suggest no genetic causal relationship between TI and CA(IVW:OR=1.10,95%CI:0.59–2.05,P=0.772).Similarly,there is no genetic causal association between GTI and CA(IVW:OR=1.07,95%CI:0.91–1.26,P=0.388),HTI and CA(IVW:OR=1.00,95%CI:0.89–1.13,P=0.943),or RTI and CA(IVW:OR=1.02,95%CI:0.96–1.09,P=0.472).Conclusion:There is no genetic causal relationship between TI and CA,and the different types of tea do not change this result.Further MR analysis is needed to investigate whether there is a potential genetic causal association between the quantity of TI and CA.
文摘Background:Previous studies have suggested a potential risk-reducing effect of tea intake(TI)on diabetes.However,the specific impacts of TI on different types of diabetes and its underlying mechanisms remain unclear.To further explore this topic,we conducted a comprehensive investigation to assess the causal relationship between TI and various types of diabetes,as well as its effects on blood glucose(Glu)and glycated hemoglobin(HbA1).Methods:We collected genome-wide association study data for TI,diabetes,type 1 diabetes(T1D),type 2 diabetes(T2D),Glu,HbA1,green tea intake,herbal tea intake,and Rooibos tea intake from the IEU database.Subsequently,we performed two-sample Mendelian randomization analysis using the TwoSampleMR package.Results:Our analysis revealed no evidence of a causal relationship between TI and the incidence of diabetes,T1D,blood Glu,HbA1c,or T2D.Similarly,no genetic causal relationship was found between green tea intake and diabetes,T1D,T2D,Glu,or HbA1c.The same applied to herbal tea intake and Rooibos tea intake,as there was no genetic causal link with diabetes,T1D,T2D,Glu,or HbA1c.Conclusion:Based on our findings,there is no indication of a causal relationship between TI and the incidence of all types of diabetes,regardless of the specific tea type.However,to comprehensively understand the potential effects of TI on diabetes incidence,including the quantity and timing of intake,further evaluation through additional Mendelian randomization studies is warranted.
基金by grants from the Jiangsu Province 333 High-level Talent Training Project(Grant No.LGY2016010)the Nanjing Science and Technology Development Plan(Grant No.201715003)the Jiangsu Province Six Talent Peaks(Grant No.WSN-030).
文摘Dear Editor,Observational studies in epidemiology have identified a correlation between hypothyroidism and cholelithiasis[1–2].However,the causal relationship between the two diseases remains unclear.To investigate the potential causal relationship,we employed a two-sample bidirectional Mendelian randomization(MR)analysis.
基金supported by the National Natural Science Foundation of China(grant number 82070994 and 82371089)the National Key Research and Development Program of China(grant number 2022YFC3502503).
文摘Objective The association between myopia and diabetic retinopathy(DR)is unclear,with inconsistent results reported,and whether the association represents causality remains unknown.This study aimed to investigate the causal associations of genetically determined myopia with DR,and further explore specific mechanisms.Methods We conducted two-sample mendelian randomization(MR)analyses of any myopia and high myopia on six DR phenotypes,including any DR,background DR,severe background DR,proliferative DR(PDR),diabetic maculopathy and unspecific DR in the primary study.Mechanism exploration of spherical equivalent refraction(SER),corneal curvature(CC)and axial length(AL)on any DR was carried out subsequently.Single-nucleotide polymorphisms(SNPs),used as genetic instruments,were derived from UK Biobank,Genetic Epidemiology Research on Adult Health and Aging cohort(GERA)and FinnGen.The inverse variance weighted(IVW)method was mainly used to assess the causality,and was complemented with sensitivity analyses and causality direction analyses.Results Using SNPs that have excluded possible confounders,we discovered suggestive and positive causal associations of any myopia with any DR(IVW:odds ratio[OR]=1.133,95%confidence interval[95%CI]:1.070-1.201,P=1.91×10^(-5))and PDR(IVW:OR=1.182,95%CI:1.088-1.285,P=8.31×10^(-5)).Similar but more significant associations were found of high myopia with any DR and PDR(IVW:OR=1.107,95%CI:1.051-1.166,P=1.39×10^(-4);OR=1.163,95%CI:1.088-1.244,P=8.76×10^(-6),respectively).Further mechanism analyses found only AL,rather than SER or CC,was strongly and significantly associated with any DR.These associations were robust in sensitivity analyses and causality direction analyses.Conclusions We found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR,which might be related with AL,indicating the significance of myopia control for preventing DR development and progression.
文摘Biliary tract cancer(BTC)seriously endangers human health.Recently,with the increasing development of therapeutic strategies,exploration of novel targeted and prognostic biomarkers has become a promising field of study(1).Newly developed biomarker signatures by Zhu et al.at the Biomarker Research significantly provide the potential prognostic and predictive values of the gut microbiome and metabolites for clinical outcomes in the management of patients with BTC(2).
基金funded by National Key Research and De velopment Program of China(No.2022YFC2703803,No.2022YFC2703001,No.2021YFC2700603)National Natural Science Foundation of China(No.82088102,No.82171613,No.82171688)+5 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-064)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Key Discipline Construction Project(2023-2025)of Three-Year Initiative Plan for Strengthening Public Health System Con struction in Shanghai(GWVI-11.1-35)Shanghai Clinical Re search Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital System Diseases Research Center(2022ZZ01012)Shanghai Frontiers Science Research Center of Reproduction and Development,Zhejiang Province College Student Science and Technology Innovation Program(Xinmiao Plan)(2023R401210).
文摘Background and Objectives:Previous studies have reported there were associations between ovarian function and dietary factors,metabolic factors and gut microbiota.However,it is unclear whether causal associations exist.We aimed to explore the causal relationship of these factors with risk of primary ovarian failure(POF).Methods and Study Design:Two-sample Mendelian randomization(MR)analysis was performed to genetically predict the causal effects of dietary and metabolic factors and gut microbiota on POF.The inverse variance weighted(IVW)method was used as the primary statistical method.A series of sensitivity analyses,including weighted median,MR-Egger,simple mode,weighted mode methods,and leave-one-out analysis,were conducted to assess the robustness of the MR analysis results.Results:IVW analysis revealed that cigarettes smoked per day,coffee intake and cooked vegetable intake were not causally correlated with POF at the genetic level.However,POF were associated with fresh fruit intake,BMI,Eubacterium(hallii group),Eubacterium(ventriosum group),Ad lercreutzia,Intestinibacter,Lachnospiraceae(UCG008),and Terrisporobacter.These findings were robust ac cording to extensive sensitivity analyses.Conclusions:This study identified several dietary factors,metabolic factors and gut microbiota taxa that may be causally implicated in POF,potentially offering new therapeutic tar gets.
基金National Natural Science Foundation of China(No.81303095)Tianjin Graduate Student Research and Innovation Project(YJSKC-20231031).
文摘Objective:To investigate the causal relationship between blood metabolite levels and the occurrence of prostate cancer by using two-sample Mendelian randomization method.Methods:Pooled data from public databases for genome-wide association analyses of blood metabolites and prostate cancer were selected,and inverse variance weighting(IVW)was used as the primary method for estimating the causal effects,while heterogeneity tests,gene multiplicity tests and sensitivity analyses were performed to assess the stability and reliability of the results.Results:A total of six known metabolites were found to potentially increase the risk of prostate cancer development(P<0.05),namely fructose,allantoin,5-hydroxytryptophan,potassium ketoisocaproate,glycyltryptophan,and 1-heptadecanoyl-glycerol-3-phosphorylcholine,with no heterogeneity or genetic pleiotropy found.Conclusion:Six known blood metabolites may be potential risk factors for prostate cancer development in European populations.
基金supported by the grants from 2023 Provincial Key Talent Project,Construction of Innovative Research Platform for Multimodal Imaging and Neuromodulation in Epilepsy in Gansu Province,2023.05-2024.05,funding 400,000,under research,presided over,Second Hospital of Lanzhou UniversityGansu Province Joint Research Fund General Project,Research on Brain Network Mechanisms of Epilepsy and its Co-morbidities Based on Crossmodal Functional Imaging,2024.01-2026.12,funding 200,000,under research,presided over,the Second Hospital of Lanzhou UniversityThe Second Hospital of Lanzhou University,"Cuiying Science and Technology Innovation"project,based on rTMS,tDCS stimulation state of adolescent myoclonic epilepsy brain network and neural loop mechanism research,CY2023-MS-B03,2024.01-2026.12,funding 100,000,in research,presided over,the Second Hospital of Lanzhou University.Hospital of Lanzhou University。
文摘Background Studies on the association between oxidative stress and epilepsy have yielded varied results.In this study,we aimed to investigate the causal relationship between oxidative stress markers and epilepsy.Methods A bidirectional two-sample Mendelian randomization(MR)study was performed based on publicly available statistics from genome-wide association studies.To explore the causal efects,single nucleotide polymorphisms were selected as instrumental variables.Inverse-variance weighted method was performed for primary analysis,supplemented by weighted median,MR-Egger,simple mode,and weighted mode.Furthermore,sensitivity analyses were performed to detect heterogeneity and pleiotropy.Results Our results showed that part of the oxidative stress biomarkers are associated with epilepsy and its subtypes.Zinc is associated with increased risk of epilepsy and generalized epilepsy(odds ratio[OR]=1.064 and 1.125,respectively).Glutathione transferase is associated with increased risk of generalized epilepsy(OR=1.055),while albumin is associated with decreased risk of generalized epilepsy(OR=0.723).Inverse MR analysis revealed that epilepsy is associated with increased levels of uric acid and total bilirubin(beta=1.266 and 0.081,respectively),as well as decreased zinc level(beta=−0.278).Furthermore,generalized epilepsy is associated with decreased ascorbate and retinol levels(beta=−0.029 and−0.038,respectively).Conclusions Our study presented novel evidence of potential causal relationships between oxidative stress and epilepsy,suggesting potential therapeutic targets for epilepsy.
