Tan Yao, Yin Jiayang, Cao Jiamin, Xie Bingyu, Zhang Feng, Xiong Wei
Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha City 410013, China.
Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha City 410013, China.
J Endocr Soc. 2023 Nov 30;8(1):bvad149. doi: 10.1210/jendso/bvad149. eCollection 2023 Dec 1.
Graves disease (GD) is a prevalent autoimmune disorder with a complex etiology. The association between serum metabolites and GD remains partially understood.
This study aimed to elucidate the causal connections between serum metabolites and predisposition to GD, examining potential genetic interplay.
A 1-sample Mendelian randomization (MR) study was conducted on the GD analysis that included 2836 cases and 374 441 controls. We utilized genome-wide association study summary data from the FinnGen project, analyzing the causal impact of 486 serum metabolites on GD. Approaches used were the inverse variance weighted methodology, Cochran's Q test, MR-Egger regression, MR-PRESSO, Steiger test, and linkage disequilibrium score regression analyses to assess genetic influence on metabolites and GD.
19 metabolites were identified as having a pronounced association with GD risk, of which 10 maintained noteworthy correlations after stringent sensitivity assessments. Three metabolites exhibited significant heritability: kynurenine (OR 3.851, = 6.09 × 10), a risk factor; glycerol 2-phosphate (OR 0.549, = 3.58 × 10) and 4-androsten-3beta,17beta-diol disulfate 2 (OR 0.461, = 1.34 × 10) were recognized as protective factors against GD. Crucially, all 3 exhibited no shared genetic interrelation with GD, further substantiating their potential causal significance in the disease.
This study unveils pivotal insights into the intricate relationships between serum metabolites and GD risk. By identifying specific risk and protective factors, it opens avenues for more precise disease understanding and management. The findings underline the importance of integrating genomics with metabolomics to fathom the multifaceted nature of GD.
格雷夫斯病（GD）是一种常见的自身免疫性疾病，病因复杂。血清代谢物与GD之间的关联仍部分未明。
本研究旨在阐明血清代谢物与GD易感性之间的因果关系，并研究潜在的基因相互作用。
对包括2836例病例和374441例对照的GD分析进行单样本孟德尔随机化（MR）研究。我们利用了芬兰基因项目的全基因组关联研究汇总数据，分析了486种血清代谢物对GD的因果影响。所采用的方法包括逆方差加权法、 Cochr an's Q检验、MR-Egger回归、MR-PRESSO、Steiger检验以及连锁不平衡评分回归分析，以评估基因对代谢物和GD的影响。
19种代谢物被确定与GD风险有显著关联，其中10种在严格的敏感性评估后仍保持显著相关性。三种代谢物表现出显著的遗传力：犬尿氨酸（OR 3.851，= 6.09×10），为风险因素；2-磷酸甘油（OR 0.549，= 3.58×10）和4-雄烯-3β，17β-二醇二硫酸酯2（OR 0.461，= 1.34×10）被认为是预防GD的保护因素。至关重要的是，这三种代谢物与GD均无共同的遗传关联，进一步证实了它们在该疾病中的潜在因果意义。
本研究揭示了血清代谢物与GD风险之间复杂关系的关键见解。通过识别特定风险和保护因素，为更精确地理解和管理该疾病开辟了道路。研究结果强调了将基因组学与代谢组学相结合以深入了解GD多方面性质的重要性。
