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免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联--一项孟德尔随机化研究
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作者 孟晓妮 曹维杰 +6 位作者 刘迪 Isinta Maranga Elijah 邢薇佳 侯海峰 徐希柱 宋曼殳 王友信 《Engineering》 SCIE EI CAS CSCD 2023年第7期74-88,I0004,共16页
既往研究已发现免疫球蛋白G(immunoglobulin G,IgG)N-糖基化与代谢特征之间存在关联,但它们之间是否存在因果关联尚有待研究。本研究使用孟德尔随机化(Mendelian randomization,MR)研究方法整合全基因组关联研究(genome-wide associatio... 既往研究已发现免疫球蛋白G(immunoglobulin G,IgG)N-糖基化与代谢特征之间存在关联,但它们之间是否存在因果关联尚有待研究。本研究使用孟德尔随机化(Mendelian randomization,MR)研究方法整合全基因组关联研究(genome-wide association studies,GWAS)和数量性状基因座(quantitative trait loci,QTL)数据探究IgG N-糖基化与代谢特征之间的双向因果关联。在正向MR分析中,通过整合IgG N-糖基-QTL遗传变异与GWAS数据和代谢特征进行分析,分别发现59个包括影响体质指数(body mass index,BMI)的9个IgG N-糖基(glycan peaks,GP)(GP1和GP6等)和影响空腹血糖(fasting plasma glucose,FPG)的7个IgG N-糖基(GP1和GP5等)以及15个[包括影响BMI的5个IgG N-糖基(GP2和GP11等)和影响FPG的4个IgG N-糖基(GP1和GP10等)]由遗传决定的IgG N-糖基在单样本和两样本MR研究中与代谢特征存在因果关联(全部P<0.05)。相应地,对整合代谢特征-QTL-遗传变异与GWAS结果和IgG N-糖基进行MR分析的结果显示,在单样本和两样本MR研究中,分别发现72个包括影响GP1的1个因果代谢特征[高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)]和影响GP2的5个因果代谢特征[FPG、收缩压(systolic blood pressure,SBP)等]和4个[包括影响GP3的1个因果代谢特征(HDL-C)和影响GP9的1个代谢特征(HDL-C)]由遗传决定的代谢特征与IgG N-糖基之间存在因果关联(全部P<0.05)。值得注意的是,在单样本和两样本的MR分析中均发现了遗传决定的高水平的GP11与BMI水平增高存在因果关联[固定效应模型-Beta(SE):0.106(0.034)和0.010(0.005)]和高水平的HDL-C与GP9水平降低存在因果关联[-0.071(0.022)和-0.306(0.151)],且这一结果在单样本和两样本的meta汇总分析中得到了进一步验证[固定效应模型-Beta(95%置信区间)分别为:0.0109(0.0012,0.0207)和-0.0759(-0.1186,-0.0332)]。综上所述,本研究全面的双向MR分析提供了IgG N-糖基化与代谢特征之间双向因果关联的证据,在一定程度上揭示了IgG N-糖基化与代谢特征之间的生物学机制。 展开更多
关键词 Mendelian randomization study Immunoglobulin G N-glycosylation Metabolic traits Quantitative trait loci Bidirectional causality
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Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population
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作者 CAO Ming Yang LIU Di +3 位作者 ZHANG Xiao Yu TIAN Qiu Yue ZHANG Qun WANG You Xin 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2022年第2期126-132,共7页
Objective Traditional epidemiological studies have shown that C-reactive protein(CRP)is associated with the risk of cardiovascular diseases(CVDs).However,whether this association is causal remains unclear.Therefore,Me... Objective Traditional epidemiological studies have shown that C-reactive protein(CRP)is associated with the risk of cardiovascular diseases(CVDs).However,whether this association is causal remains unclear.Therefore,Mendelian randomization(MR)was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke,atrial fibrillation,arrhythmia and congestive heart failure.Methods We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken(JENGER),and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables.MR estimates were calculated with the inverse-variance weighted(IVW),penalized weighted median and weighted median.MR-Egger regression was used to explore pleiotropy.Results No significant causal association of genetically determined CRP level with ischemic stroke,atrial fibrillation or arrhythmia was found with all four MR methods(all Ps>0.05).The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure(OR:1.337,95%CI:1.005–1.780,P=0.046),whereas the other three methods did not.No clear pleiotropy or heterogeneity were observed.Conclusions Suggestive evidence was found only in analysis of congestive heart failure;therefore,further studies are necessary.Furthermore,no causal association was found between CRP and the other three cardiovascular outcomes. 展开更多
关键词 Mendelian randomization C-reactive protein Cardiovascular diseases East Asians Causal inference
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