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
BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whethe...BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whether the observations are causal because of confounding factors.AIM To investigate the causal associations between urate levels and IBD using bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental variables from published genome-wide association studies(GWASs).Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD(the UK Biobank,the FinnGen database and a large GWAS meta-analysis)and one for urate levels(a large GWAS meta-analysis).MR analyses included the inverse-variance-weighted method,weighted-median estimator,MR-Egger and sensitivity analyses(MR-PRESSO).A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.RESULTS Genetically higher serum urate levels were strongly associated with an increased risk of UC[odds ratio(OR):1.95,95%confidence interval(CI):1.86-2.05]after outlier correction,and the ORs(95%CIs)for IBD and CD were 0.94(95%CI:0.86-1.03)and 0.91(95%CI:0.80-1.04),respectively.Animal studies have confirmed the positive association between urate levels and UC.Moreover,genetically predicted IBD was inversely related to urate levels(OR:0.97,95%CI:0.94-0.99).However,no association was observed between genetically influenced UC or CD and urate levels.CONCLUSION Urate levels might be risk factors for UC,whereas genetically predicted IBD was inversely associated with urate levels.These findings provide essential new insight for treating and preventing IBD.展开更多
BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to invest...BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.展开更多
BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been hig...BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.展开更多
BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations ar...BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations are causal.METHODS To explore the relationship between dietary intake and the risk of GERD,we extracted appropriate single nucleotide polymorphisms from genome-wide asso-ciation study data on 24 dietary intakes.Three methods were adopted for data analysis:Inverse variance weighting,weighted median methods,and MR-Egger's method.The odds ratio(OR)and 95%confidence interval(CI)were used to eva-luate the causal association between dietary intake and GERD.RESULTS Our univariate Mendelian randomization(UVMR)results showed significant evidence that pork intake(OR,2.83;95%CI:1.76-4.55;P=1.84×10–5),beer intake(OR,2.70,95%CI:2.00-3.64;P=6.54×10–11),non-oily fish intake(OR,2.41;95%CI:1.49-3.91;P=3.59×10–4)have a protective effect on GERD.In addition,dried fruit intake(OR,0.37;95%CI:0.27-0.50;6.27×10–11),red wine intake(OR,0.34;95%CI:0.25-0.47;P=1.90×10-11),cheese intake(OR,0.46;95%CI:0.39-0.55;P=3.73×10-19),bread intake(OR,0.72;95%CI:0.56-0.92;P=0.0009)and cereal intake(OR,0.45;95%CI:0.36-0.57;P=2.07×10-11)were negatively associated with the risk of GERD.There was a suggestive asso-ciation for genetically predicted coffee intake(OR per one SD increase,1.22,95%CI:1.03-1.44;P=0.019).Multi-variate Mendelian randomization further confirmed that dried fruit intake,red wine intake,cheese intake,and cereal intake directly affected GERD.In contrast,the impact of pork intake,beer intake,non-oily fish intake,and bread intake on GERD was partly driven by the common risk factors for GERD.However,after adjusting for all four elements,there was no longer a suggestive association between coffee intake and GERD.CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD,providing new insights for the treatment and prevention of GERD.展开更多
BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nuc...BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyl...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.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
lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,t...lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.展开更多
BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown...BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown.AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies(GWAS)of the European population were identified as genetic instrument variants.GWAS statistics for individuals with UC(6968 patients and 20464 controls;adults)and CD(5956 patients and 14927 controls;adults)were obtained from the International IBD Genetics Consortium.GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium(2565 patients and 14745 controls;adults)and FinnGen project(20992 patients and 197800 controls;adults),respectively.Inverse-variance weighted was applied to assess the causal relationship,and the results were strengthened by heterogeneity,pleiotropy and leave-one-out analyses.RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety[odds ratio:1.071(95%confidence interval:1.009-1.135),P=0.023],while genetic susceptibility to CD was not associated with anxiety.Genetic susceptibility to anxiety was not associated with UC or CD.No heterogeneity or pleiotropy was observed,and the leave-one-out analysis excluded the potential influence of a particular variant.CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.展开更多
Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomizatio...Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.展开更多
BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the ...BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.展开更多
BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth facto...BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth factor(IGF)family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.assess genetic relationships between IGF family members and AF.METHODS MR was performed based on genome-wide association study(GWAS)datasets,and concentration levels of 14 IGF family members were retrieved.An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations.A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects.Two-sample MR packages were used to perform MR analysis in R.MR-Egger,weighted median(WM),and inverse va-riance weighted(IVW)methods were used.RESULTS Core Tip:Due to the high prevalence of atrial fibrillation(AF),and adverse outcomes related to it,it is important to identify risk factors associated with development of the condition.Insulin-like growth factor(IGF)family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.The results of the current study provide novel insights on the pathogenesis of AF,and implic-ations of serum IGF family member concentrations when assessing the risk of AF.The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF.Further observational and experimental studies are critically needed.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
BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in...BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.展开更多
BACKGROUND The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes.AIM To determine whether cheese consumption was causal...BACKGROUND The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes.AIM To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy.METHODS This was a two-sample Mendelian randomized(MR)study.Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database.MR analysis was conducted using inverse variance weighting.For sensitivity analyses,MR-Egger regression,weighted median,weighted mode,and leave-one-out methods were conducted.A fixed-effect model was used to meta-analyze two sample MR estimates.The traits of gestational hypertension were pregnancy hypertension(123579 individuals)and oedema,proteinuria and hypertensive disorders in pregnancy,childbirth and the puerperium(123579 individuals),and traits of gestational diabetes were gestational diabetes(123579 individuals)and diabetes mellitus in pregnancy(116363 individuals),respectively.RESULTS Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension[odds ratio(OR)=0.60,95%confidence interval(CI):0.47-0.76,P<0.001]and gestational diabetes(OR=0.41,95%CI:0.30-0.55,P<0.001)in inverse variance weighted analysis.Sensitivity analysis showed no heterogeneity(all P>0.05)nor horizontal pleiotropy(all P>0.05)in the relationship between cheese intake and gestational hypertension,but heterogeneity presented(all P<0.05)in relation to gestational diabetes in the two-sample MR analysis.CONCLUSION Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis,suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.展开更多
BACKGROUND Observational studies have suggested that depression is associated with sarcopenia.However,the causal relationship between depression and sarcopenia remains unclear.AIM To investigate the causal relationshi...BACKGROUND Observational studies have suggested that depression is associated with sarcopenia.However,the causal relationship between depression and sarcopenia remains unclear.AIM To investigate the causal relationship between depression and sarcopenia.METHODS We performed a Mendelian randomization(MR)analysis to identify the bidirectional relationship between depression and sarcopenia-related traits.Summarylevel data and independent variants used as instrumental variables came from large genome-wide association studies of depression(414055 cases and 892299 controls),of appendicular lean mass(ALM,450243 participants),and of hand grip strength(exposure:360000 participants;outcome:334925 participants).RESULTS We identified a negative association of depression with lower ALM[odds ratio(OR):0.932,95%confidence interval(95%CI):0.889-0.979,P=0.005].In the reverse MR analysis,we also observed an inverse association of hand grip strength with depression(OR:0.200,95%CI:0.108-0.370,P<0.001).Similar results were obtained in sensitivity analyses.CONCLUSION Depression was causally related to decreased muscle mass,and declined muscle strength might lead to a higher risk of depression.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:This study utilizes the two-sample Mendelian randomization method to examine the correlations between 196 variants of gut microbiota and sepsis.Methods:This study leveraged summary statistics data from the ...Background:This study utilizes the two-sample Mendelian randomization method to examine the correlations between 196 variants of gut microbiota and sepsis.Methods:This study leveraged summary statistics data from the genome-wide association studies on gut microbiota and sepsis,obtained from MiBioGen(n=18340)and the UK Biobank(n=462918).Following pre-determined P-value and clumping thresholds,independently significant SNPs associated with the abundance of 196 gut microbiota were selected as instrumental variables.The primary methodology for the Mendelian randomization study involved the inverse-variance weighting method,with results being assessed based on the odds ratio and a 95%confidence interval.To assure the solidity of our findings,we executed an array of sensitivity analyses,encompassing the Mendelian randomization-Egger intercept test,Mendelian randomization pleiotropy residual sum and outlier test,Cochran’s Q test,and the leave-one-out test.Results:An elevated presence of Bifidobacterium may diminish sepsis risk(odds ratio=0.79;95%confidence interval 0.72–0.86;P=5.19e–07).No signs of heterogeneity or pleiotropy were exhibited in the sensitivity analysis.Conclusion:Bifidobacterium may be instrumental in reducing sepsis risk.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
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Supported by National Natural Science Foundation of China,No.82170567,No.81873546,No.82170568,and No.82300627Program of Shanghai Academic/Technology Research Leader,No.22XD1425000+4 种基金The"Shu Guang"project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation,No.19SG30,ChinaDeep Blue Project of Naval Medical University(Pilot Talent Plan)The Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission,No.22CGA42The Shanghai Sailing Program,No.23YF1458600and Shanghai Natural Science Foundation,No.23ZR1478700.
文摘BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whether the observations are causal because of confounding factors.AIM To investigate the causal associations between urate levels and IBD using bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental variables from published genome-wide association studies(GWASs).Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD(the UK Biobank,the FinnGen database and a large GWAS meta-analysis)and one for urate levels(a large GWAS meta-analysis).MR analyses included the inverse-variance-weighted method,weighted-median estimator,MR-Egger and sensitivity analyses(MR-PRESSO).A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.RESULTS Genetically higher serum urate levels were strongly associated with an increased risk of UC[odds ratio(OR):1.95,95%confidence interval(CI):1.86-2.05]after outlier correction,and the ORs(95%CIs)for IBD and CD were 0.94(95%CI:0.86-1.03)and 0.91(95%CI:0.80-1.04),respectively.Animal studies have confirmed the positive association between urate levels and UC.Moreover,genetically predicted IBD was inversely related to urate levels(OR:0.97,95%CI:0.94-0.99).However,no association was observed between genetically influenced UC or CD and urate levels.CONCLUSION Urate levels might be risk factors for UC,whereas genetically predicted IBD was inversely associated with urate levels.These findings provide essential new insight for treating and preventing IBD.
基金Supported by National Natural Science Foundation of China(General Program),No.82070631.
文摘BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.
基金Supported by Science and Technology Research Project of Sichuan Administration of Traditional Chinese Medicine,No.2023MS419.
文摘BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.
文摘BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations are causal.METHODS To explore the relationship between dietary intake and the risk of GERD,we extracted appropriate single nucleotide polymorphisms from genome-wide asso-ciation study data on 24 dietary intakes.Three methods were adopted for data analysis:Inverse variance weighting,weighted median methods,and MR-Egger's method.The odds ratio(OR)and 95%confidence interval(CI)were used to eva-luate the causal association between dietary intake and GERD.RESULTS Our univariate Mendelian randomization(UVMR)results showed significant evidence that pork intake(OR,2.83;95%CI:1.76-4.55;P=1.84×10–5),beer intake(OR,2.70,95%CI:2.00-3.64;P=6.54×10–11),non-oily fish intake(OR,2.41;95%CI:1.49-3.91;P=3.59×10–4)have a protective effect on GERD.In addition,dried fruit intake(OR,0.37;95%CI:0.27-0.50;6.27×10–11),red wine intake(OR,0.34;95%CI:0.25-0.47;P=1.90×10-11),cheese intake(OR,0.46;95%CI:0.39-0.55;P=3.73×10-19),bread intake(OR,0.72;95%CI:0.56-0.92;P=0.0009)and cereal intake(OR,0.45;95%CI:0.36-0.57;P=2.07×10-11)were negatively associated with the risk of GERD.There was a suggestive asso-ciation for genetically predicted coffee intake(OR per one SD increase,1.22,95%CI:1.03-1.44;P=0.019).Multi-variate Mendelian randomization further confirmed that dried fruit intake,red wine intake,cheese intake,and cereal intake directly affected GERD.In contrast,the impact of pork intake,beer intake,non-oily fish intake,and bread intake on GERD was partly driven by the common risk factors for GERD.However,after adjusting for all four elements,there was no longer a suggestive association between coffee intake and GERD.CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD,providing new insights for the treatment and prevention of GERD.
基金Supported by National Natural Science Foundation of China,No.U21A20411.
文摘BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.
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The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.
基金Supported by China Postdoctoral Science Foundation,No.2021M701614Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111063,No.2022A1515111045Foundation of Guangdong Provincial People’s Hospital,No.8200010545。
文摘BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown.AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies(GWAS)of the European population were identified as genetic instrument variants.GWAS statistics for individuals with UC(6968 patients and 20464 controls;adults)and CD(5956 patients and 14927 controls;adults)were obtained from the International IBD Genetics Consortium.GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium(2565 patients and 14745 controls;adults)and FinnGen project(20992 patients and 197800 controls;adults),respectively.Inverse-variance weighted was applied to assess the causal relationship,and the results were strengthened by heterogeneity,pleiotropy and leave-one-out analyses.RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety[odds ratio:1.071(95%confidence interval:1.009-1.135),P=0.023],while genetic susceptibility to CD was not associated with anxiety.Genetic susceptibility to anxiety was not associated with UC or CD.No heterogeneity or pleiotropy was observed,and the leave-one-out analysis excluded the potential influence of a particular variant.CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.
基金supported by grants from the Natural Science Foundation of China(No.82102199)the General Program of Shanghai Municipal Commission of Health and Family Planning(No.202040479).
文摘Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.
基金supported by grants from Hainan Provincial Natural Science Foundation of China(821RC557,2019RC232)National Natural Science Foundation of China(81871611,82160647)+1 种基金Finance Science and Technology Program of Sichuan Province(2022YFS0602)Hainan Clinical Medical Research Center Project(LCYX202310)。
文摘BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.
文摘BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth factor(IGF)family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.assess genetic relationships between IGF family members and AF.METHODS MR was performed based on genome-wide association study(GWAS)datasets,and concentration levels of 14 IGF family members were retrieved.An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations.A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects.Two-sample MR packages were used to perform MR analysis in R.MR-Egger,weighted median(WM),and inverse va-riance weighted(IVW)methods were used.RESULTS Core Tip:Due to the high prevalence of atrial fibrillation(AF),and adverse outcomes related to it,it is important to identify risk factors associated with development of the condition.Insulin-like growth factor(IGF)family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.The results of the current study provide novel insights on the pathogenesis of AF,and implic-ations of serum IGF family member concentrations when assessing the risk of AF.The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF.Further observational and experimental studies are critically needed.
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Supported by the Huzhou Science and Technology Plan,No.2022GY27.
文摘BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.
文摘BACKGROUND The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes.AIM To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy.METHODS This was a two-sample Mendelian randomized(MR)study.Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database.MR analysis was conducted using inverse variance weighting.For sensitivity analyses,MR-Egger regression,weighted median,weighted mode,and leave-one-out methods were conducted.A fixed-effect model was used to meta-analyze two sample MR estimates.The traits of gestational hypertension were pregnancy hypertension(123579 individuals)and oedema,proteinuria and hypertensive disorders in pregnancy,childbirth and the puerperium(123579 individuals),and traits of gestational diabetes were gestational diabetes(123579 individuals)and diabetes mellitus in pregnancy(116363 individuals),respectively.RESULTS Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension[odds ratio(OR)=0.60,95%confidence interval(CI):0.47-0.76,P<0.001]and gestational diabetes(OR=0.41,95%CI:0.30-0.55,P<0.001)in inverse variance weighted analysis.Sensitivity analysis showed no heterogeneity(all P>0.05)nor horizontal pleiotropy(all P>0.05)in the relationship between cheese intake and gestational hypertension,but heterogeneity presented(all P<0.05)in relation to gestational diabetes in the two-sample MR analysis.CONCLUSION Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis,suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.
基金Zhejiang Province Traditional Chinese Medicine Science and Technology Project,No.2023ZR075.
文摘BACKGROUND Observational studies have suggested that depression is associated with sarcopenia.However,the causal relationship between depression and sarcopenia remains unclear.AIM To investigate the causal relationship between depression and sarcopenia.METHODS We performed a Mendelian randomization(MR)analysis to identify the bidirectional relationship between depression and sarcopenia-related traits.Summarylevel data and independent variants used as instrumental variables came from large genome-wide association studies of depression(414055 cases and 892299 controls),of appendicular lean mass(ALM,450243 participants),and of hand grip strength(exposure:360000 participants;outcome:334925 participants).RESULTS We identified a negative association of depression with lower ALM[odds ratio(OR):0.932,95%confidence interval(95%CI):0.889-0.979,P=0.005].In the reverse MR analysis,we also observed an inverse association of hand grip strength with depression(OR:0.200,95%CI:0.108-0.370,P<0.001).Similar results were obtained in sensitivity analyses.CONCLUSION Depression was causally related to decreased muscle mass,and declined muscle strength might lead to a higher risk of depression.
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.
基金supported by Intramural Project of The First Affiliated Hospital of Guangxi University of Chinese Medicine(2018QN008).
文摘Background:This study utilizes the two-sample Mendelian randomization method to examine the correlations between 196 variants of gut microbiota and sepsis.Methods:This study leveraged summary statistics data from the genome-wide association studies on gut microbiota and sepsis,obtained from MiBioGen(n=18340)and the UK Biobank(n=462918).Following pre-determined P-value and clumping thresholds,independently significant SNPs associated with the abundance of 196 gut microbiota were selected as instrumental variables.The primary methodology for the Mendelian randomization study involved the inverse-variance weighting method,with results being assessed based on the odds ratio and a 95%confidence interval.To assure the solidity of our findings,we executed an array of sensitivity analyses,encompassing the Mendelian randomization-Egger intercept test,Mendelian randomization pleiotropy residual sum and outlier test,Cochran’s Q test,and the leave-one-out test.Results:An elevated presence of Bifidobacterium may diminish sepsis risk(odds ratio=0.79;95%confidence interval 0.72–0.86;P=5.19e–07).No signs of heterogeneity or pleiotropy were exhibited in the sensitivity analysis.Conclusion:Bifidobacterium may be instrumental in reducing sepsis risk.
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.
