Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsist...Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.展开更多
Background The potential modifiable factors influencing irritable bowel syndrome(IBS)have not been thoroughly documented.We aimed to systematically investigate the modifiable factors associated with IBS,while accounti...Background The potential modifiable factors influencing irritable bowel syndrome(IBS)have not been thoroughly documented.We aimed to systematically investigate the modifiable factors associated with IBS,while accounting for the impact of unobserved confounders and coexisting disorders.Methods Genetic correlation and Mendelian randomisation(MR)analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS.Subsequently,multiresponse MR(MR2)was employed to further examine these associations.Summary-level genome-wide association data were used.Modifiable factors and coexisting disorders(ie,gastrointestinal and psychiatric disorders)were identified based on evidence from cohort studies and meta-analysis.In all analyses,IBS was the primary outcome,while in the MR2 analysis,coexisting disorders were also treated as outcomes alongside IBS.Results Most identified modifiable factors and coexisting disorders exhibited genetic correlations with IBS.MR analyses revealed strong causation between IBS and multisite chronic pain(OR=2.20,95%CI 1.82 to 2.66),gastro-oesophageal reflux disease(OR=1.31,95%CI 1.23 to 1.39),well-being spectrum(OR=0.17,95%CI 0.13 to 0.21),life satisfaction(OR=0.31,95%CI 0.25 to 0.38),positive affect(OR=0.30,95%CI 0.24 to 0.37),neuroticism score(OR=1.20,95%CI 1.16 to 1.25)and depression(OR=1.50,95%CI 1.37 to 1.66).Additionally,smoking,alcohol frequency,college or university degree,intelligence,childhood maltreatment,frailty index,diverticular disease of the intestine and schizophrenia were suggestively associated with IBS.Robust associations were found between multisite chronic pain and both IBS and coexisting disorders.Conclusions Our study identified a comprehensive array of potential modifiable factors and coexisting disorders associated with IBS,supported by genetic evidence,including genetic correlation and multiple MR analyses.The presence of multisite chronic pain may offer a promising avenue for the concurrent prevention of IBS and its coexisting disorders.展开更多
基金supported by the China Postdoctoral Science Foundation(Grant No.2021M703366)Shenzhen Science and Technology Program(Grant No.KQTD20190929172835662).
文摘Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
基金China Postdoctoral Science Foundation(Grant No.2021M703366)the Shenzhen Science and Technology Program(Grant No.KQTD20190929172835662)athe Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB38040200).The funders had no role in the study design,data analysis,interpretation of data,or preparation of the manuscript.
文摘Background The potential modifiable factors influencing irritable bowel syndrome(IBS)have not been thoroughly documented.We aimed to systematically investigate the modifiable factors associated with IBS,while accounting for the impact of unobserved confounders and coexisting disorders.Methods Genetic correlation and Mendelian randomisation(MR)analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS.Subsequently,multiresponse MR(MR2)was employed to further examine these associations.Summary-level genome-wide association data were used.Modifiable factors and coexisting disorders(ie,gastrointestinal and psychiatric disorders)were identified based on evidence from cohort studies and meta-analysis.In all analyses,IBS was the primary outcome,while in the MR2 analysis,coexisting disorders were also treated as outcomes alongside IBS.Results Most identified modifiable factors and coexisting disorders exhibited genetic correlations with IBS.MR analyses revealed strong causation between IBS and multisite chronic pain(OR=2.20,95%CI 1.82 to 2.66),gastro-oesophageal reflux disease(OR=1.31,95%CI 1.23 to 1.39),well-being spectrum(OR=0.17,95%CI 0.13 to 0.21),life satisfaction(OR=0.31,95%CI 0.25 to 0.38),positive affect(OR=0.30,95%CI 0.24 to 0.37),neuroticism score(OR=1.20,95%CI 1.16 to 1.25)and depression(OR=1.50,95%CI 1.37 to 1.66).Additionally,smoking,alcohol frequency,college or university degree,intelligence,childhood maltreatment,frailty index,diverticular disease of the intestine and schizophrenia were suggestively associated with IBS.Robust associations were found between multisite chronic pain and both IBS and coexisting disorders.Conclusions Our study identified a comprehensive array of potential modifiable factors and coexisting disorders associated with IBS,supported by genetic evidence,including genetic correlation and multiple MR analyses.The presence of multisite chronic pain may offer a promising avenue for the concurrent prevention of IBS and its coexisting disorders.
