循环氨基酸与重症肌无力的因果关联评估:一项双向孟德尔随机化研究  

Assessing the Causal Association of Circulating Amino Acids With Myasthenia Gravis:A Bi-Directional Mendelian Randomization Study

作　　者：臧虎 汲晓宇 祝畅[1] 姚文龙[1] 万里[1] 刘彤彤 ZANG Hu;JI Xiaoyu;ZHU Chang;YAO Wenlong;WAN Li;LIU Tongtong(Department of Anesthesiology,Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health,and Wuhan Clinical Research Center for Geriatric Anesthesia,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉学与疼痛医学科,老年麻醉与围术期脑健康湖北省重点实验室,武汉市老年麻醉临床医学研究中心,武汉430030

出　　处：《医药导报》2025年第3期440-445,共6页Herald of Medicine

基　　金：国家自然科学基金资助项目(82201387)。

摘　　要：目的利用孟德尔随机化方法探讨循环氨基酸水平与重症肌无力(MG)风险之间的双向因果关联。方法使用公开的全基因组关联研究(GWASs)遗传数据进行两样本孟德尔随机化分析,利用不同来源的GWASs数据进行验证以评估结果稳健性。运用5种模型进行两样本双向孟德尔随机化分析,采用比值比(OR)评价循环中9种氨基酸水平与MG风险之间的因果关系。采用敏感性分析、异质性检验和多效性检验评估结果的稳健性。以逆方差加权法(IVW)估算的因果效应为主要结果,使用不同GWASs来源的数据对IVW估算的因果效应进行验证,以进一步评估结果稳健性。结果遗传预测较高的循环谷氨酰胺水平与较低的MG风险显著相关[OR(95%CI)=0.696(0.524,0.926),P=0.0127,IVW]。采用不同GWASs验证分析表明,遗传预测的较高循环谷氨酰胺水平与MG风险显著负相关[OR(95%CI)=0.321(0.178,0.581),P=1.67×10^(-1),IVW]。此外,遗传预测较高MG风险与较低循环谷氨酰胺和丙氨酸水平相关(分别为-0.178±0.009,P=0.049;-0.013±0.007,P=0.048,IVW)。结论通过遗传学方法揭示循环氨基酸水平与MG患病风险之间具有潜在双向因果关系。需要进一步研究来阐明循环氨基酸水平与MG之间的作用机制。Objective To investigate the bidirectional causal relationship between circulating amino acid levels and the risk of myasthenia gravis(MG)using Mendelian randomization(MR).Methods A two-sample Mendelian randomization analysis was conducted using publicly available genome-wide association study(GWAS)genetic data,with validation from GWAS data from different sources to assess the robustness of the results.Five models were used for the two-sample bidirectional MR analysis,and odds ratios(OR)were calculated to evaluate the causal relationship between the levels of nine circulating amino acids and MG risk.Sensitivity analyses,heterogeneity tests,and pleiotropy tests were performed to assess the robustness of the results.The causal effect estimated by the inverse variance weighted(IVW)method was the primary result,and the IVW-estimated causal effects were further validated using data from different GWAS sources to assess robustness.Results Genetically predicted higher circulating glutamine levels were significantly associated with a lower risk of MG[OR(95%CI)=0.696(0.524,0.926),P=0.0127,IVW model].Validation analyses using GWAS data from various sources also demonstrated a significant negative association between genetically predicted higher circulating glutamine levels and MG risk[OR(95%CI)=0.321(0.178,0.581),P=1.67×10^(-1),IVW model].Moreover,genetically predicted higher MG risk was associated with lower levels of circulating glutamine and alanine(β=-0.178±0.009,P=0.049;β=-0.013±0.007,P=0.048,IVW model,respectively).Conclusion Genetic evidence reveals a potential bidirectional causal relationship between circulating amino acid levels and MG risk.Further studies are required to elucidate the mechanisms underlying this relationship.

关 键 词：重症肌无力 两样本双向孟德尔随机化 循环氨基酸水平 因果关系 

分 类 号：R746[医药卫生—神经病学与精神病学] R18[医药卫生—临床医学]