Assessing the Causal Association of Circulating Amino Acids With Myasthenia Gravis:A Bi-Directional Mendelian Randomization Study
10.3870/j.issn.1004-0781.2025.03.018
- VernacularTitle: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
- Author:
Hu ZANG
1
;
Xiaoyu JI
1
;
Chang ZHU
1
;
Wenlong YAO
1
;
Li WAN
1
;
Tongtong LIU
1
Author Information
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
- Publication Type:Journal Article
- Keywords:
Myasthenia gravis;
Bi-Directional mendelian randomization;
Circulating amino acids levels;
Causal associa-tion
- From:
Herald of Medicine
2025;44(3):440-445
- CountryChina
- Language:Chinese
-
Abstract:
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 a-nalysis 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 anal-ysis,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 high-er circulating glutamine levels were significantly associated with a lower risk of MG[OR(95％CI)=0.696(0.524,0.926),P=0.012 7,IVW model].Validation analyses using GWAS data from various sources also demonstrated a significant negative associa-tion between genetically predicted higher circulating glutamine levels and MG risk[OR(95％CI)=0.321(0.178,0.581),P=1.67x10-1,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.
