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
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
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^(-6)for hypothyroidism;ORIVW=1.08,95%CI=1.04–1.12,P=8.14×10^(-5)for 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
Background:Cutaneous leukocytoclastic angiitis(CLA)is a clinically rele-vant condition,with previous studies suggesting an association with herpes virus infections.However,the causality of this association remains unc...Background:Cutaneous leukocytoclastic angiitis(CLA)is a clinically rele-vant condition,with previous studies suggesting an association with herpes virus infections.However,the causality of this association remains unclear.This study aimed to investigate the causal relationship between herpes viruses and CLA.Methods:Genetic variants linked to the herpes virus were retrieved from the Integrative Epidemiology Unit at the University of Bristol open genome-wide association studies project and FinnGen database.Data on CLA,involving 262 CLA cases and 207,482 healthy controls,were obtained from the FinnGen consortium R7.Mendelian randomization(MR)analysis,including the inverse variance weighted(IVW),MR-Egger,and weighted median methods,was performed.Sensitivity analyzes were conducted to ensure the accuracy of the results.Results:Of the 15 herpes viruses investigated,only human herpes virus 6(HHV-6)demonstrated a causal association with CLA(odds ratio:1.886,95%confidence interval:1.053–3.378,p=0.033),indicating that HHV-6 infection significantly increases the risk of CLA.Furthermore,IVW and MR-Egger tests for heterogeneity confirmed homogeneous MR analysis results without evi-dence of horizontal pleiotropy(p>0.05).No significant causal relationship was observed for other herpes viruses,such as herpes simplex virus,varicella-zoster virus,cytomegalovirus,and Epstein-Barr virus.Conclusion:Our MR analyzes strongly support a causal relationship between HHV-6 and CLA,elucidating the etiology of this condition and highlighting the potential of HHV-6-targeted therapeutic interventions in CLA treatment.However,further research is necessary to expound the underlying mechanisms and explore potential therapeutic interventions targeting HHV-6-associated CLA.展开更多
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
BACKGROUND Although there is currently a wealth of evidence to indicate that maternal educational attainment is associated with gestational diabetes mellitus(GDM),the specific modifiable risk factors that mediate the ...BACKGROUND Although there is currently a wealth of evidence to indicate that maternal educational attainment is associated with gestational diabetes mellitus(GDM),the specific modifiable risk factors that mediate the causal relationship between these two variables have yet to be identified.AIM To identify the specific modifiable risk factors that mediate the causal relationship between the level of maternal education and GDM.METHODS Mendelian randomization(MR)was conducted using data from genome-wide association studies of European populations.We initially performed a two-sample MR analysis using data on genetic variants associated with the duration of education as instruments,and subsequently adopted a two-step MR approach using metabolic and lifestyle factors as mediators to examine the mechanisms underlying the relationship between the level of maternal education and risk of developing GDM.In addition,we calculated the proportions of total causal effects mediated by identified metabolic and lifestyle factors.RESULTS A genetically predicted higher educational attainment was found to be associated with a lower risk of developing GDM(OR:0.71,95%CI:0.60-0.84).Among the metabolic factors assessed,four emerged as potential mediators of the education-GDM association,which,ranked by mediated proportions,were as follows:Waist-to-hip-ratio(31.56%,95%CI:12.38%-50.70%),body mass index(19.20%,95%CI:12.03%-26.42%),high-density lipoprotein cholesterol(12.81%,95%CI:8.65%-17.05%),and apolipoprotein A-1(7.70%,95%CI:4.32%-11.05%).These findings proved to be robust to sensitivity analyses.CONCLUSION Our findings indicate a causal relationship between lower levels of maternal education and the risk of developing GDM can be partly explained by adverse metabolic profiles.展开更多
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(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=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(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=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
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
AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-base...AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND,with protein data derived from two independent large-scale proteomics datasets.Potential drug targets were identified using Bayesian colocalization,followed by MR analysis,sensitivity testing,and external validation.Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.RESULTS:The study identified six promising protein targets,each successfully replicated at least twice.The results included three proteins related to diabetic retinopathy(ICAM1,GCKR,WARS),two proteins related to age-related macular degeneration(WARS,BRD2),and two proteins related to glaucoma(SVEP1,NPTXR).Additionally,drug prediction and molecular docking indicated that five drugs(fenofibrate,trofinetide,ticagrelor,lifitegrast,acetaminophen)effectively bound to the target proteins.CONCLUSION:This study identified six potential protein targets for RND and five existing drugs with therapeutic potential.By integrating plasma proteomics with genetic data,it provides a cost-effective framework for drug discovery.展开更多
Objective:This study aimed to explore the causal link between olive intake and the occurrence of coronary heart disease(CHD)using Mendelian randomization(MR).Methods:In this study,genome-wide association study data fr...Objective:This study aimed to explore the causal link between olive intake and the occurrence of coronary heart disease(CHD)using Mendelian randomization(MR).Methods:In this study,genome-wide association study data from IEU OpenGWAS were employed.A 2-sample MR analysis was used to determine the causal association of olive intake with CHD and cardiovascular outcomes(myocardial infarction,heart failure,stroke,and death due to cardiac causes).The data for olive intake included 64,949 samples and 9,851,867 single nucleotide polymorphisms(SNPs),the data for CHD included 361,194 samples and 13,295,130 SNPs;The data for myocardial infarction included 361,194 samples and 12,640,541 SNPs,the heart failure include 208,178 samples and 16,380,422 SNPs,the data for stroke included 361,194 samples and 12,404,026 SNPs,and the data for death due to cardiac causes included 361,194 samples and 10,071,648 SNPs.Additionally,a 2-step,2-sample MR approach was used for mediation analysis to determine whether lipid traits mediate the causal association between olive intake and CHD.The data for total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein B,and apolipoprotein A1 included 115,078 samples and 12,321,875 SNPs,while the data for triglycerides included 21,545 samples and 11,871,391 SNPs.Cochran’s Q test was applied to examine potential heterogeneity,and the MR-Egger method was used to assess horizontal pleiotropy among SNPs.Leave-one-out analysis was performed as a sensitivity analysis to evaluate the robustness of the results.Results:For each standard deviation increase in olive intake,the risk of CHD decreased by a substantial 1.9%(odds ratio(OR)=0.981,95%confidence interval(CI):0.963 to 0.998,P=0.031),the risk of myocardial infarction was significantly reduced by 1.6%(OR=0.984,95%CI:0.969 to 0.999,P=0.032),and the risk of heart failure declined by 62.1%(OR=0.379,95%CI:0.192 to 0.746,P=0.005).Furthermore,mediation analysis with MR indicated that lipid traits did not mediate the causal relationship between olive intake and CHD.Conclusion:There is a negative correlation between olive intake and the incidence of CHD,and this relationship is not mediated by lipid traits.Olive intake was also negatively associated with some cardiovascular outcomes,suggesting that increasing olive intake holds significant value in preventing the onset and progression of CHD.展开更多
Background:Hypertension and non-alcoholic fatty liver disease(NAFLD)share several pathophysiologic risk factors,and the exact relationship between the two remains unclear.Our study aims to provide evidence concerning ...Background:Hypertension and non-alcoholic fatty liver disease(NAFLD)share several pathophysiologic risk factors,and the exact relationship between the two remains unclear.Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey(NHANES)2017-2018 and Mendelian randomization(MR)analyses.Methods:Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018.Subsequently,a two-sample MR study was performed using the genome-wide association study(GWAS)summary statistics to identify the causal association between hypertension,systolic blood pressure(SBP),diastolic blood pressure(DBP),and NAFLD.The primary inverse variance weighted(IVW)and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD.Sensitivity analyses were adopted to confirm the robustness of the results.Results:A total of 3144 participants were enrolled for our observational study in NHANES.Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk(odds ratio[OR]=1.677;95%confidence interval[CI],1.159-2.423).SBP≥130 mmHg and DBP≥80 mmHg were also significantly positively correlated with NAFLD.Moreover,hypertension was independently connected with liver steatosis(β=7.836[95%CI,2.334-13.338]).The results of MR analysis also supported a causal association between hypertension(OR=7.203[95%CI,2.297-22.587])and NAFLD.Similar results were observed for the causal exploration between SBP(OR=1.024[95%CI,1.003-1.046]),DBP(OR=1.047[95%CI,1.005-1.090]),and NAFLD.The sensitive analysis further confirmed the robustness and reliability of these findings(all P>0.05).Conclusion:Hypertension was associated with an increased risk of NAFLD.展开更多
Obstructive sleep apnea(OSA)is often a lifestyle disease associated with obesity,which is rapidly evolving as a major health concern with diverse multisystemic implications.To prevent and mitigate its adverse effects ...Obstructive sleep apnea(OSA)is often a lifestyle disease associated with obesity,which is rapidly evolving as a major health concern with diverse multisystemic implications.To prevent and mitigate its adverse effects and reduce its burden on society,its aetiopathogeneses must be precisely understood.Numerous studies focusing on the range of diverse anatomic,functional,and lifestyle factors have already been carried out to determine the possible contributory roles of these factors in OSA.Recently,evidence to validate the role of inflammatory pathways and immune mechanisms in the aetiopathogeneses of OSA is being developed.This allows for further research and translation of such knowledge for targeted therapeutic and preventive interventions in patients with or who are at risk of developing OSA.展开更多
Background Previous studies have found that patients with epilepsy are more likely to sufer impulsivity.However,the causal relationship between impulsivity and epilepsy is unknown.In this study,we conduct a bidirectio...Background Previous studies have found that patients with epilepsy are more likely to sufer impulsivity.However,the causal relationship between impulsivity and epilepsy is unknown.In this study,we conduct a bidirectional Mendelian randomization(MR)study to explore the causal relationship between impulsivity and epilepsy with recurrent seizure.Methods Data of the genome-wide association studies(GWAS)on 14 impulsivity traits and epilepsy were obtained from the GWAS catalog and UK Biobank.Inverse-variance weighted(IVW)and weighted median(WM)methods were utilized for MR estimates.IVW,MR-Egger regression,and MR-pleiotropy residual sum and outlier(MR-PRESSO)methods were used to assess heterogeneity and pleiotropy.Results Single-nucleotide polymorphisms(SNPs)related to the lack of perseverance were associated with a decreased risk of epilepsy with recurrent seizures according to the results of IVW(odd ratio[OR]=0.93,95%confdent interval[CI]=0.90-0.97,P=0.001)and WM(OR=0.93,95%CI=0.87-0.98,P=0.007).Meanwhile,heterogeneity was not observed with a Cochran Q-derived P value of 0.819 for MR egger and a P value of 0.808 for IVW.Pleiotropy was not found according to the MR-PRESSO(P=0.273).The other 13 impulsivity traits had no causal efect on epilepsy with recurrent seizures.Meanwhile,SNPs related with epilepsy with recurrent seizures had no causal efect on the 14 impulsivity traits.Conclusions This MR study suggests that lack of perseverance may be a protective factor against epilepsy with recurrent seizures.However,epilepsy with recurrent seizures does not afect impulsivity.展开更多
Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association b...Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization(MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial.A two-sample MR was performed to assess the causal association,using summary statistics from the Atrial Fibrillation Genetics Consortium(n=537,409)and the Global Lipids Genetics Consortium(n=188,577).The clinical measures of thyroid function include thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)levels,FT3:FT4 ratio and concentration of thyroid peroxidase antibodies(TPOAb).The serum lipid metabolism traits include total cholesterol(TC)and triglycerides,high-density lipoprotein,and low-density lipoprotein(LDL)levels.The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC(β=0.052,P=0.002)and LDL(β=0.041,P=0.018)levels.In addition,the FT3:FT4 ratio was significantly associated with TC(β=0.240,P=0.033)and LDL(β=0.025,P=0.027)levels.However,no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together,the results of the present study suggest an association between thyroid function and serum lipid metabolism,highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.展开更多
Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(...Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(MR)study to examine the potential causal effect between OA and CVD.Methods:Exposures were self-reported OA,knee osteoarthritis(KOA),and hip osteoarthritis(HOA).The outcomes were 12 CVDs,including heart failure,atrial fibrillation,coronary artery disease,pulmonary embolism,stroke and its subtypes,myocardial infarction,coronary heart disease,and primary hypertension.All outcomes were obtained from published genomewide association studies.The inverse-variance weighted method was used as the primary MR analysis.Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results.Results:Self-reported OA increased the incidence of small vessel stroke(odds ratio[OR]=1.25,95%confidence interval[CI]:1.02–1.52,p=0.03)and primary hypertension(1.01[1.00–1.02],p<0.01).HOA increased the incidence of stroke(1.06[1.01–1.11],p=0.02)and two subtypes(cardioembolic stroke:1.12[1.02–1.23],p=0.02;ischemic stroke:1.06[1.01–1.11],p=0.03).Patients with KOA had an increased risk of heart failure(1.10[1.04–1.16],p<0.01),atrial fibrillation(1.08[1.02–1.13],p<0.01),small vessel stroke(1.21[1.06–1.39],p=0.01),and primary hypertension(1.01[1.01–1.02],p<0.01).Conclusions:Patients with OA have an increased risk of several CVDs.The causality of this relationship may have clinical implications for improving the quality of prevention and treatment.展开更多
基金Supported by the National Natural Science Foundation of China(No.81960174)the Natural Science Foundation of Guangxi Zhuang Autonomous Region(No.2023GXNSFAA026154)the Youth Science Foundation of Guangxi Medical University(No.GXMUYSF201912).
文摘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.
文摘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.
基金funded by the National Natural Science Foundation of China(Grant Nos.82220108002 to F.C.,82273737 to R.Z.,82473728 to Y.W.)the US National Institutes of Health(Grant Nos.CA209414,HL060710,ES000002 to D.C.C.,CA209414,CA249096 to Y.L.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).R.Z.was partially supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young-Level Academic Leadership Training Program of Nanjing Medical University.
文摘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^(-6)for hypothyroidism;ORIVW=1.08,95%CI=1.04–1.12,P=8.14×10^(-5)for 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.
基金The Natural Science Foundation of Shanxi Province,Grant/Award Number:202203021221269The National Natural Science Foundation of China,Grant/Award Number:82001740。
文摘Background:Cutaneous leukocytoclastic angiitis(CLA)is a clinically rele-vant condition,with previous studies suggesting an association with herpes virus infections.However,the causality of this association remains unclear.This study aimed to investigate the causal relationship between herpes viruses and CLA.Methods:Genetic variants linked to the herpes virus were retrieved from the Integrative Epidemiology Unit at the University of Bristol open genome-wide association studies project and FinnGen database.Data on CLA,involving 262 CLA cases and 207,482 healthy controls,were obtained from the FinnGen consortium R7.Mendelian randomization(MR)analysis,including the inverse variance weighted(IVW),MR-Egger,and weighted median methods,was performed.Sensitivity analyzes were conducted to ensure the accuracy of the results.Results:Of the 15 herpes viruses investigated,only human herpes virus 6(HHV-6)demonstrated a causal association with CLA(odds ratio:1.886,95%confidence interval:1.053–3.378,p=0.033),indicating that HHV-6 infection significantly increases the risk of CLA.Furthermore,IVW and MR-Egger tests for heterogeneity confirmed homogeneous MR analysis results without evi-dence of horizontal pleiotropy(p>0.05).No significant causal relationship was observed for other herpes viruses,such as herpes simplex virus,varicella-zoster virus,cytomegalovirus,and Epstein-Barr virus.Conclusion:Our MR analyzes strongly support a causal relationship between HHV-6 and CLA,elucidating the etiology of this condition and highlighting the potential of HHV-6-targeted therapeutic interventions in CLA treatment.However,further research is necessary to expound the underlying mechanisms and explore potential therapeutic interventions targeting HHV-6-associated CLA.
基金Supported by Xi’an Science and Technology Program Project(No.24YXYJ0108)Support Projects of Xi’an Children’s Hospital(No.2024I07).
文摘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.
文摘BACKGROUND Although there is currently a wealth of evidence to indicate that maternal educational attainment is associated with gestational diabetes mellitus(GDM),the specific modifiable risk factors that mediate the causal relationship between these two variables have yet to be identified.AIM To identify the specific modifiable risk factors that mediate the causal relationship between the level of maternal education and GDM.METHODS Mendelian randomization(MR)was conducted using data from genome-wide association studies of European populations.We initially performed a two-sample MR analysis using data on genetic variants associated with the duration of education as instruments,and subsequently adopted a two-step MR approach using metabolic and lifestyle factors as mediators to examine the mechanisms underlying the relationship between the level of maternal education and risk of developing GDM.In addition,we calculated the proportions of total causal effects mediated by identified metabolic and lifestyle factors.RESULTS A genetically predicted higher educational attainment was found to be associated with a lower risk of developing GDM(OR:0.71,95%CI:0.60-0.84).Among the metabolic factors assessed,four emerged as potential mediators of the education-GDM association,which,ranked by mediated proportions,were as follows:Waist-to-hip-ratio(31.56%,95%CI:12.38%-50.70%),body mass index(19.20%,95%CI:12.03%-26.42%),high-density lipoprotein cholesterol(12.81%,95%CI:8.65%-17.05%),and apolipoprotein A-1(7.70%,95%CI:4.32%-11.05%).These findings proved to be robust to sensitivity analyses.CONCLUSION Our findings indicate a causal relationship between lower levels of maternal education and the risk of developing GDM can be partly explained by adverse metabolic profiles.
文摘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(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=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(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=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.
基金supported by the National Natural Science Foundation of China[No.81871823,81971583,81671652,8207090113]National Key R&D Program of China[No.2018YFC1312900]+3 种基金Natural Science Foundation of Shanghai[No.20ZR1406400]Science and Technology Commission of Shanghai Municipality[No.18JC1410403]Shanghai Municipal Science and Technology Major Project[No.2017SHZDZX01,2018SHZDZX01]Shanghai Science and Technology Committee[No.22dz1204700].
文摘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.
基金Supported by the National Natural Science Foundation of China(No.82000919)Science and Technology Project of Education Department of Jilin Province(No.JJKH20201089KJ).
文摘AIM:To employ proteome-wide Mendelian randomization(MR)to explore novel protein and drug targets for retinal neurodegenerative diseases(RND)in individuals of European ancestry.METHODS:This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND,with protein data derived from two independent large-scale proteomics datasets.Potential drug targets were identified using Bayesian colocalization,followed by MR analysis,sensitivity testing,and external validation.Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.RESULTS:The study identified six promising protein targets,each successfully replicated at least twice.The results included three proteins related to diabetic retinopathy(ICAM1,GCKR,WARS),two proteins related to age-related macular degeneration(WARS,BRD2),and two proteins related to glaucoma(SVEP1,NPTXR).Additionally,drug prediction and molecular docking indicated that five drugs(fenofibrate,trofinetide,ticagrelor,lifitegrast,acetaminophen)effectively bound to the target proteins.CONCLUSION:This study identified six potential protein targets for RND and five existing drugs with therapeutic potential.By integrating plasma proteomics with genetic data,it provides a cost-effective framework for drug discovery.
基金supported by the National Natural Science Foundation of China(81860073 and 82360076)Application foundation project of Yunnan Province(202001AT070039 and 202401AT070069)+4 种基金Special Foundation Projects of Joint Applied Basic Research of Yunnan Provincial Department of Science and Technology with Kunming Medical University(2019FE001(-138))Young Talents of Yunnan Thousand Talents Plan(RLQN20200002)Yunnan Health Training Project of High-Level Talents(H-2018032)Young and Middle-aged Academic Leaders and Reserve Candidates of Kunming Medical University(J13397031)The Innovation Fund Project for Postgraduate Education of Kunming Medical University in 2025(2025S073).
文摘Objective:This study aimed to explore the causal link between olive intake and the occurrence of coronary heart disease(CHD)using Mendelian randomization(MR).Methods:In this study,genome-wide association study data from IEU OpenGWAS were employed.A 2-sample MR analysis was used to determine the causal association of olive intake with CHD and cardiovascular outcomes(myocardial infarction,heart failure,stroke,and death due to cardiac causes).The data for olive intake included 64,949 samples and 9,851,867 single nucleotide polymorphisms(SNPs),the data for CHD included 361,194 samples and 13,295,130 SNPs;The data for myocardial infarction included 361,194 samples and 12,640,541 SNPs,the heart failure include 208,178 samples and 16,380,422 SNPs,the data for stroke included 361,194 samples and 12,404,026 SNPs,and the data for death due to cardiac causes included 361,194 samples and 10,071,648 SNPs.Additionally,a 2-step,2-sample MR approach was used for mediation analysis to determine whether lipid traits mediate the causal association between olive intake and CHD.The data for total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein B,and apolipoprotein A1 included 115,078 samples and 12,321,875 SNPs,while the data for triglycerides included 21,545 samples and 11,871,391 SNPs.Cochran’s Q test was applied to examine potential heterogeneity,and the MR-Egger method was used to assess horizontal pleiotropy among SNPs.Leave-one-out analysis was performed as a sensitivity analysis to evaluate the robustness of the results.Results:For each standard deviation increase in olive intake,the risk of CHD decreased by a substantial 1.9%(odds ratio(OR)=0.981,95%confidence interval(CI):0.963 to 0.998,P=0.031),the risk of myocardial infarction was significantly reduced by 1.6%(OR=0.984,95%CI:0.969 to 0.999,P=0.032),and the risk of heart failure declined by 62.1%(OR=0.379,95%CI:0.192 to 0.746,P=0.005).Furthermore,mediation analysis with MR indicated that lipid traits did not mediate the causal relationship between olive intake and CHD.Conclusion:There is a negative correlation between olive intake and the incidence of CHD,and this relationship is not mediated by lipid traits.Olive intake was also negatively associated with some cardiovascular outcomes,suggesting that increasing olive intake holds significant value in preventing the onset and progression of CHD.
基金supported by the Wuhan University Education&Development Foundation(No.2002330)the National Stem Cell Clinical Research Project of China.
文摘Background:Hypertension and non-alcoholic fatty liver disease(NAFLD)share several pathophysiologic risk factors,and the exact relationship between the two remains unclear.Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey(NHANES)2017-2018 and Mendelian randomization(MR)analyses.Methods:Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018.Subsequently,a two-sample MR study was performed using the genome-wide association study(GWAS)summary statistics to identify the causal association between hypertension,systolic blood pressure(SBP),diastolic blood pressure(DBP),and NAFLD.The primary inverse variance weighted(IVW)and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD.Sensitivity analyses were adopted to confirm the robustness of the results.Results:A total of 3144 participants were enrolled for our observational study in NHANES.Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk(odds ratio[OR]=1.677;95%confidence interval[CI],1.159-2.423).SBP≥130 mmHg and DBP≥80 mmHg were also significantly positively correlated with NAFLD.Moreover,hypertension was independently connected with liver steatosis(β=7.836[95%CI,2.334-13.338]).The results of MR analysis also supported a causal association between hypertension(OR=7.203[95%CI,2.297-22.587])and NAFLD.Similar results were observed for the causal exploration between SBP(OR=1.024[95%CI,1.003-1.046]),DBP(OR=1.047[95%CI,1.005-1.090]),and NAFLD.The sensitive analysis further confirmed the robustness and reliability of these findings(all P>0.05).Conclusion:Hypertension was associated with an increased risk of NAFLD.
文摘Obstructive sleep apnea(OSA)is often a lifestyle disease associated with obesity,which is rapidly evolving as a major health concern with diverse multisystemic implications.To prevent and mitigate its adverse effects and reduce its burden on society,its aetiopathogeneses must be precisely understood.Numerous studies focusing on the range of diverse anatomic,functional,and lifestyle factors have already been carried out to determine the possible contributory roles of these factors in OSA.Recently,evidence to validate the role of inflammatory pathways and immune mechanisms in the aetiopathogeneses of OSA is being developed.This allows for further research and translation of such knowledge for targeted therapeutic and preventive interventions in patients with or who are at risk of developing OSA.
文摘Background Previous studies have found that patients with epilepsy are more likely to sufer impulsivity.However,the causal relationship between impulsivity and epilepsy is unknown.In this study,we conduct a bidirectional Mendelian randomization(MR)study to explore the causal relationship between impulsivity and epilepsy with recurrent seizure.Methods Data of the genome-wide association studies(GWAS)on 14 impulsivity traits and epilepsy were obtained from the GWAS catalog and UK Biobank.Inverse-variance weighted(IVW)and weighted median(WM)methods were utilized for MR estimates.IVW,MR-Egger regression,and MR-pleiotropy residual sum and outlier(MR-PRESSO)methods were used to assess heterogeneity and pleiotropy.Results Single-nucleotide polymorphisms(SNPs)related to the lack of perseverance were associated with a decreased risk of epilepsy with recurrent seizures according to the results of IVW(odd ratio[OR]=0.93,95%confdent interval[CI]=0.90-0.97,P=0.001)and WM(OR=0.93,95%CI=0.87-0.98,P=0.007).Meanwhile,heterogeneity was not observed with a Cochran Q-derived P value of 0.819 for MR egger and a P value of 0.808 for IVW.Pleiotropy was not found according to the MR-PRESSO(P=0.273).The other 13 impulsivity traits had no causal efect on epilepsy with recurrent seizures.Meanwhile,SNPs related with epilepsy with recurrent seizures had no causal efect on the 14 impulsivity traits.Conclusions This MR study suggests that lack of perseverance may be a protective factor against epilepsy with recurrent seizures.However,epilepsy with recurrent seizures does not afect impulsivity.
基金supported by the National Natural Science Foundation of China(No.81825003,91957123)the Peking University Start-up Grant(BMU2018YJ002)+1 种基金High-performance Computing Platform of Peking University and Beijing Technology and Business University Grant(No.88442Y0033)Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in Patients with Atherosclerotic Cardiovascular Diseases(NCT03606824)。
文摘Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization(MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial.A two-sample MR was performed to assess the causal association,using summary statistics from the Atrial Fibrillation Genetics Consortium(n=537,409)and the Global Lipids Genetics Consortium(n=188,577).The clinical measures of thyroid function include thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)levels,FT3:FT4 ratio and concentration of thyroid peroxidase antibodies(TPOAb).The serum lipid metabolism traits include total cholesterol(TC)and triglycerides,high-density lipoprotein,and low-density lipoprotein(LDL)levels.The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC(β=0.052,P=0.002)and LDL(β=0.041,P=0.018)levels.In addition,the FT3:FT4 ratio was significantly associated with TC(β=0.240,P=0.033)and LDL(β=0.025,P=0.027)levels.However,no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together,the results of the present study suggest an association between thyroid function and serum lipid metabolism,highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
基金The National Natural Science Foundation of China,Grant/Award Number:82001740Natural Science Foundation of Shanxi Province,Grant/Award Number:202203021221269。
文摘Background:Epidemiological studies have shown a close association between osteoarthritis(OA)and cardiovascular disease(CVD),but reliable evidence needs to be provided.We performed a two-sample Mendelian randomization(MR)study to examine the potential causal effect between OA and CVD.Methods:Exposures were self-reported OA,knee osteoarthritis(KOA),and hip osteoarthritis(HOA).The outcomes were 12 CVDs,including heart failure,atrial fibrillation,coronary artery disease,pulmonary embolism,stroke and its subtypes,myocardial infarction,coronary heart disease,and primary hypertension.All outcomes were obtained from published genomewide association studies.The inverse-variance weighted method was used as the primary MR analysis.Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results.Results:Self-reported OA increased the incidence of small vessel stroke(odds ratio[OR]=1.25,95%confidence interval[CI]:1.02–1.52,p=0.03)and primary hypertension(1.01[1.00–1.02],p<0.01).HOA increased the incidence of stroke(1.06[1.01–1.11],p=0.02)and two subtypes(cardioembolic stroke:1.12[1.02–1.23],p=0.02;ischemic stroke:1.06[1.01–1.11],p=0.03).Patients with KOA had an increased risk of heart failure(1.10[1.04–1.16],p<0.01),atrial fibrillation(1.08[1.02–1.13],p<0.01),small vessel stroke(1.21[1.06–1.39],p=0.01),and primary hypertension(1.01[1.01–1.02],p<0.01).Conclusions:Patients with OA have an increased risk of several CVDs.The causality of this relationship may have clinical implications for improving the quality of prevention and treatment.
