In the practical environment,it is very common for the simultaneous occurrence of base excitation and crosswind.Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascina...In the practical environment,it is very common for the simultaneous occurrence of base excitation and crosswind.Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascinating.For this purpose,the effects of the wind speed and random excitation level are investigated with the stochastic averaging method(SAM)based on the energy envelope.The results of the analytical prediction are verified with the Monte-Carlo method(MCM).The numerical simulation shows that the introduction of wind can reduce the critical excitation level for triggering an inter-well jump and make a bi-stable energy harvester(BEH)realize the performance enhancement for a weak base excitation.However,as the strength of the wind increases to a particular level,the influence of the random base excitation on the dynamic responses is weakened,and the system exhibits a periodic galloping response.A comparison between a BEH and a linear energy harvester(LEH)indicates that the BEH demonstrates inferior performance for high-speed wind.Relevant experiments are conducted to investigate the validity of the theoretical prediction and numerical simulation.The experimental findings also show that strong random excitation is favorable for the BEH in the range of low wind speeds.However,as the speed of the incoming wind is up to a particular level,the disadvantage of the BEH becomes clear and evident.展开更多
The travel time of rock compressional waves is an essential parameter used for estimating important rock properties,such as porosity,permeability,and lithology.Current methods,like wireline logging tests,provide broad...The travel time of rock compressional waves is an essential parameter used for estimating important rock properties,such as porosity,permeability,and lithology.Current methods,like wireline logging tests,provide broad measurements but lack finer resolution.Laboratory-based rock core measurements offer higher resolution but are resource-intensive.Conventionally,wireline logging and rock core measurements have been used independently.This study introduces a novel approach that integrates both data sources.The method leverages the detailed features from limited core data to enhance the resolution of wireline logging data.By combining machine learning with random field theory,the method allows for probabilistic predictions in regions with sparse data sampling.In this framework,12 parameters from wireline tests are used to predict trends in rock core data.The residuals are modeled using random field theory.The outcomes are high-resolution predictions that combine both the predicted trend and the probabilistic realizations of the residual.By utilizing unconditional and conditional random field theories,this method enables unconditional and conditional simulations of the underlying high-resolution rock compressional wave travel time profile and provides uncertainty estimates.This integrated approach optimizes the use of existing core and logging data.Its applicability is confirmed in an oil project in West China.展开更多
BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
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 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
Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle...Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle Glaucoma (POAG). Methods: GWAS data for bibulosity, smoking, and POAG were obtained from the Social Science Genetic Association Consortium website and the IEU OpenGWAS Project website, respectively. Using a P-value threshold of −8, a linkage disequilibrium coefficient (r2) of 0.001, and a linkage disequilibrium region width of 10,000 kb, the data were aggregated, resulting in 6 SNPs for bibulosity and 253 SNPs for smoking. Three regression models, MR-Egger, Weighted Median Estimator (WME), and Random-Effects Inverse-Variance Weighted (IVW) were applied to analyze the causal impact of bibulosity and smoking on POAG. Results: The GWAS data for alcohol consumption and smoking were derived from European populations, while the GWAS data for Primary Open-Angle Glaucoma (POAG) were sourced from East Asian populations, with no gender restrictions. Analysis using three different regression models revealed that neither excessive alcohol consumption nor smoking significantly increased the risk of developing POAG. Specifically, the odds ratios with 95% confidence intervals for the alcohol consumption group were 0.854 (0.597 - 1.221) in MR-Egger regression, 0.922 (0.691 - 1.231) in WME regression, and 0.944 (0.711 - 1.252) in IVW regression. For the smoking group, the odds ratios were 1.146 (0.546 - 2.406) in MR-Egger regression, 0.850 (0.653 - 1.111) in WME regression, and 0.939 (0.780 - 1.131) in IVW regression. Given the significant heterogeneity in the SNPs associated with smoking, the focus was primarily on the results from the IVW regression model. Conclusion: Alcohol consumption and smoking are not significant risk factors for the development of POAG.展开更多
Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on su...Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.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 Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking....Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.12272355,1202520411902294)+1 种基金the Opening Foundation of Shanxi Provincial Key Laboratory for Advanced Manufacturing Technology of China(No.XJZZ202304)the Shanxi Provincial Graduate Innovation Project of China(No.2023KY629)。
文摘In the practical environment,it is very common for the simultaneous occurrence of base excitation and crosswind.Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascinating.For this purpose,the effects of the wind speed and random excitation level are investigated with the stochastic averaging method(SAM)based on the energy envelope.The results of the analytical prediction are verified with the Monte-Carlo method(MCM).The numerical simulation shows that the introduction of wind can reduce the critical excitation level for triggering an inter-well jump and make a bi-stable energy harvester(BEH)realize the performance enhancement for a weak base excitation.However,as the strength of the wind increases to a particular level,the influence of the random base excitation on the dynamic responses is weakened,and the system exhibits a periodic galloping response.A comparison between a BEH and a linear energy harvester(LEH)indicates that the BEH demonstrates inferior performance for high-speed wind.Relevant experiments are conducted to investigate the validity of the theoretical prediction and numerical simulation.The experimental findings also show that strong random excitation is favorable for the BEH in the range of low wind speeds.However,as the speed of the incoming wind is up to a particular level,the disadvantage of the BEH becomes clear and evident.
基金the Australian Government through the Australian Research Council's Discovery Projects funding scheme(Project DP190101592)the National Natural Science Foundation of China(Grant Nos.41972280 and 52179103).
文摘The travel time of rock compressional waves is an essential parameter used for estimating important rock properties,such as porosity,permeability,and lithology.Current methods,like wireline logging tests,provide broad measurements but lack finer resolution.Laboratory-based rock core measurements offer higher resolution but are resource-intensive.Conventionally,wireline logging and rock core measurements have been used independently.This study introduces a novel approach that integrates both data sources.The method leverages the detailed features from limited core data to enhance the resolution of wireline logging data.By combining machine learning with random field theory,the method allows for probabilistic predictions in regions with sparse data sampling.In this framework,12 parameters from wireline tests are used to predict trends in rock core data.The residuals are modeled using random field theory.The outcomes are high-resolution predictions that combine both the predicted trend and the probabilistic realizations of the residual.By utilizing unconditional and conditional random field theories,this method enables unconditional and conditional simulations of the underlying high-resolution rock compressional wave travel time profile and provides uncertainty estimates.This integrated approach optimizes the use of existing core and logging data.Its applicability is confirmed in an oil project in West China.
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
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.
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Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle Glaucoma (POAG). Methods: GWAS data for bibulosity, smoking, and POAG were obtained from the Social Science Genetic Association Consortium website and the IEU OpenGWAS Project website, respectively. Using a P-value threshold of −8, a linkage disequilibrium coefficient (r2) of 0.001, and a linkage disequilibrium region width of 10,000 kb, the data were aggregated, resulting in 6 SNPs for bibulosity and 253 SNPs for smoking. Three regression models, MR-Egger, Weighted Median Estimator (WME), and Random-Effects Inverse-Variance Weighted (IVW) were applied to analyze the causal impact of bibulosity and smoking on POAG. Results: The GWAS data for alcohol consumption and smoking were derived from European populations, while the GWAS data for Primary Open-Angle Glaucoma (POAG) were sourced from East Asian populations, with no gender restrictions. Analysis using three different regression models revealed that neither excessive alcohol consumption nor smoking significantly increased the risk of developing POAG. Specifically, the odds ratios with 95% confidence intervals for the alcohol consumption group were 0.854 (0.597 - 1.221) in MR-Egger regression, 0.922 (0.691 - 1.231) in WME regression, and 0.944 (0.711 - 1.252) in IVW regression. For the smoking group, the odds ratios were 1.146 (0.546 - 2.406) in MR-Egger regression, 0.850 (0.653 - 1.111) in WME regression, and 0.939 (0.780 - 1.131) in IVW regression. Given the significant heterogeneity in the SNPs associated with smoking, the focus was primarily on the results from the IVW regression model. Conclusion: Alcohol consumption and smoking are not significant risk factors for the development of POAG.
基金the Key Discipline of Zhejang Province in Public Health and Preventative Medicine(First Class,Category A)at the Hangzhou Medical College,China.
文摘Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.
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 the National Natural Science Foundation of China(grant number:81801345)Tianjin Key Medical Discipline(Specialty)Construction Project(grant number:TJYXZDXK-033A).
文摘Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.