BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The pre...BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.展开更多
目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资...目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资料齐全的浆膜腔积液细胞块95例,其中恶性84例,良性11例(对照组)。应用免疫组化方法检测浆膜腔积液细胞蜡块中Survivin、IMP3及Claudin1蛋白的表达情况,并对比分析其在良恶性浆膜腔积液以及不同恶性肿瘤中的差异。结果恶性胸膜腔积液病例中胸腔积液53例,腹腔积液31例。肺腺癌41例,消化系统腺癌25例,卵巢恶性肿瘤9例,其他恶性肿瘤9例。与对照组相比,肺腺癌组及消化系统腺癌组IMP3的表达差异具有统计学意义(P<0.05),消化系统腺癌组Claudin1的表达差异具有统计学意义(P<0.05),其他组别Survivin、IMP3及Claudin1的表达与对照组相比差异均无统计学意义(P>0.05)。结论IMP3及Claudin1在恶性浆膜腔积液判断是否为消化系统腺癌来源时具有鉴别意义,IMP3在肺腺癌来源具有鉴别意义。展开更多
基金Supported by The Guangdong Basic and Applied Basic Research Foundation,No.2023A1515011432The Guangzhou Science and Technology Planning Project,No.2023A04J0627and National Natural Science Foundation of China,No.82004256.
文摘BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.
文摘目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资料齐全的浆膜腔积液细胞块95例,其中恶性84例,良性11例(对照组)。应用免疫组化方法检测浆膜腔积液细胞蜡块中Survivin、IMP3及Claudin1蛋白的表达情况,并对比分析其在良恶性浆膜腔积液以及不同恶性肿瘤中的差异。结果恶性胸膜腔积液病例中胸腔积液53例,腹腔积液31例。肺腺癌41例,消化系统腺癌25例,卵巢恶性肿瘤9例,其他恶性肿瘤9例。与对照组相比,肺腺癌组及消化系统腺癌组IMP3的表达差异具有统计学意义(P<0.05),消化系统腺癌组Claudin1的表达差异具有统计学意义(P<0.05),其他组别Survivin、IMP3及Claudin1的表达与对照组相比差异均无统计学意义(P>0.05)。结论IMP3及Claudin1在恶性浆膜腔积液判断是否为消化系统腺癌来源时具有鉴别意义,IMP3在肺腺癌来源具有鉴别意义。
